Bio

Clinical Focus


  • Nephrology

Academic Appointments


Administrative Appointments


  • Director of Clinical Research, Stanford University School of Medicine, Division of Nephrology (2009 - Present)
  • Director of Renal Drug Evaluation and Outcomes Research, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (2004 - 2009)

Honors & Awards


  • Fellowship Teaching Award, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (2009)
  • Norman S. Coplon Extramural Research Program Award, Satellite Healthcare, Mountain View, CA (2005)
  • T. Franklin Williams Scholar, Association of Subspecialty Professors (2004)

Professional Education


  • Fellowship:Brigham and Women's Hospital Harvard Medical School (2009) MA
  • Residency:Joachim Huber MD Private Practice (1992) Austria
  • Sc.D., Harvard School of Public Health, Health Policy and Management (2001)
  • M.P.H., Harvard School of Public Health, Health Care Management (1999)
  • Residency:Kaiser Franz Josef-Spital (1999) Austria
  • Internship:Neues Evangelisches Krankenhaus Wien-Waehring (1992) Austria
  • Medical Education:University of Vienna (1990) Austria

Research & Scholarship

Current Research and Scholarly Interests


Working as a clinical nephrologist in my native Vienna, Austria, I was struck by the abysmal outcomes and quality of life experienced by the patients for whom I cared. I was equally struck by the absence of quality evidence that would guide us in our treatment of these vulnerable patients. Seeking to make a difference, I sought and underwent doctoral training in health policy and epidemiology at Harvard, with the career goal to conduct high quality research that would fill important evidence gaps in our field. At Brigham and Women’s Hospital, I joined the Division of Pharmacoepidemiology where I learned from some of the leaders in the field how to conduct quality comparative effectiveness research long before it became a buzz-word. My immediate colleagues and the wider environment at Harvard Medical School enabled me to master and apply the most novel analytical approaches that are necessary to tackle difficult problems in the presence of confounding by indication, a dreaded threat to validity in comparative effectiveness research. I was able to build a group of colleagues that shared a passion for drug utilization and comparative effectiveness research in kidney disease, cardiovascular disease, and diabetes, and we were able to publish our findings in leading journals.
Having recently moved to Stanford, I am in the process of building a young research group that will again focus on comparative effectiveness research. Here, I am once again in the privileged position to build on a fabulous research environment and an exquisite wealth of knowledge and experience represented by the scientists and clinicians on and off campus. With the enthusiastic support and collaborations of my colleagues here at Stanford as well as at other institutions in the U.S. and Europe, I am confident that we will provide important contributions that will guide us towards more evidence based and effective care of our patients with kidney disease. Doing so will hopefully contribute to improving the lives of these vulnerable patients, which is my explicit career goal.

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Warfarin treatment in patients with atrial fibrillation and advanced chronic kidney disease: sins of omission or commission? JAMA : the journal of the American Medical Association Winkelmayer, W. C., Turakhia, M. P. 2014; 311 (9): 913-915

    View details for DOI 10.1001/jama.2014.1781

    View details for PubMedID 24595773

  • Trends in Anemia Care in Older Patients Approaching End-Stage Renal Disease in the United States (1995-2010). JAMA internal medicine Winkelmayer, W. C., Mitani, A. A., Goldstein, B. A., Brookhart, M. A., Chertow, G. M. 2014

    Abstract

    IMPORTANCE Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation. OBJECTIVE To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD. DESIGN, SETTING, AND PARTICIPANTS Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD. EXPOSURE Time, defined as calendar year of incident ESRD. MAIN OUTCOMES AND MEASURES Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs). RESULTS Records of 466?803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR,?9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR,?9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR,?1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010. CONCLUSIONS AND RELEVANCE Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.

    View details for DOI 10.1001/jamainternmed.2014.87

    View details for PubMedID 24589911

  • Predicting the outcomes of rhabdomyolysis: a good starting point. JAMA internal medicine Wilhelm-Leen, E. R., Winkelmayer, W. C. 2013; 173 (19): 1828-1829

    View details for DOI 10.1001/jamainternmed.2013.9235

    View details for PubMedID 23999843

  • Kidney Disease and Cardiovascular Risk Whether Black or White Race Matters JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Weiner, D. E., Winkelmayer, W. C. 2013; 310 (7): 697-698

    View details for Web of Science ID 000323254500018

    View details for PubMedID 23989731

  • Treated and Untreated Kidney Failure in Older Adults What's the Right Balance? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Tamura, M. K., Winkelmayer, W. C. 2012; 307 (23): 2545-2546

    View details for Web of Science ID 000305391400033

    View details for PubMedID 22797456

  • Predialysis Nephrology Care of Older Patients Approaching End-stage Renal Disease ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Liu, J., Chertow, G. M., Tamura, M. K. 2011; 171 (15): 1371-1378

    Abstract

    Little is known about trends in the timing of first nephrology consultation and associated outcomes among older patients initiating dialysis.Data from patients aged 67 years or older who initiated dialysis in the United States between January 1, 1996, and December 31, 2006, were stratified by timing of the earliest identifiable nephrology visit. Trends of earlier nephrology consultation were formally examined in light of concurrently changing case mix and juxtaposed with trends in 1-year mortality rates after initiation of dialysis.Among 323,977 older patients initiating dialysis, the proportion of patients receiving nephrology care less than 3 months before initiation of dialysis decreased from 49.6% (in 1996) to 34.7% (in 2006). Patients initiated dialysis with increasingly preserved kidney function, from a mean estimated glomerular filtration rate of 8 mL/min/1.73 m(2) in 1996 to 12 mL/min/1.73 m(2) in 2006. Patients were less anemic in later years, which was partly attributable to increased use of erythropoiesis-stimulating agents, and fewer used peritoneal dialysis as the initial modality. During the same period, crude 1-year mortality rates remained unchanged (annual change in mortality rate, +0.2%; 95% confidence interval, 0% to +0.4%). Adjustment for changes in demographic and comorbidity patterns yielded estimated annual reductions in 1-year mortality rates of 0.9% (95% confidence interval, 0.7% to 1.1%), which were explained only partly by concurrent trends toward earlier nephrology consultation (annual mortality reduction after accounting for timing of nephrology care was attenuated to 0.4% [0.2% to 0.6%]).Despite significant trends toward earlier use of nephrology consultation among older patients approaching maintenance dialysis, we observed no material improvement in 1-year survival rates after dialysis initiation during the same time period.

    View details for Web of Science ID 000293642800013

    View details for PubMedID 21824952

  • Tackling the Achilles' Heel of Hemodialysis NEW ENGLAND JOURNAL OF MEDICINE Winkelmayer, W. C. 2011; 364 (4): 372-374

    View details for Web of Science ID 000286592600014

    View details for PubMedID 21268730

  • Comparative Mortality Risk of Anemia Management Practices in Incident Hemodialysis Patients JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Brookhart, M. A., Schneeweiss, S., Avorn, J., Bradbury, B. D., Liu, J., Winkelmayer, W. C. 2010; 303 (9): 857-864

    Abstract

    Controversy exists about optimal management of anemia in end-stage renal disease.To compare the mortality risk of different dialysis center-level patterns of anemia management.Using data from Medicare's end-stage renal disease program (1999-2007), we characterized each US dialysis center's annual anemia management practice by estimating its typical use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in hemodialysis patients within 4 hematocrit categories. We used Cox proportional hazards regression to correlate center-level patterns of ESA and iron use with 1-year mortality risk in 269,717 incident hemodialysis patients.One-year all-cause mortality.Monthly mortality rates were highest in patients with hematocrit less than 30% (mortality, 2.1%) and lowest for those with hematocrit of 36% or higher (mortality, 0.7%). After adjustment for baseline case-mix differences, dialysis centers that used larger ESA doses in patients with hematocrit less than 30% had lower mortality rates than centers that used smaller doses (highest vs lowest dose group: hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.90-0.97). Centers that administered iron more frequently to patients with hematocrit less than 33% also had lower mortality rates (highest vs lowest quintile, HR, 0.95; 95% CI, 0.91-0.98). However, centers that used larger ESA doses in patients with hematocrit between 33% and 35.9% had higher mortality rates (highest vs lowest quintile, HR, 1.07; 95% CI, 1.03-1.12). More intensive use of both ESAs and iron was associated with increased mortality risk in patients with hematocrit of 36% or higher. These findings persisted across a range of secondary analyses.Greater ESA and iron use were associated with decreased mortality risk at lower hematocrit levels, in which mortality rates are the highest. Although the overall mortality rate was lower at higher hematocrit levels, elevated mortality risk was associated with greater use of ESAs and iron in these patients.

    View details for Web of Science ID 000275059500019

    View details for PubMedID 20197532

  • Altitude and All-Cause Mortality in Incident Dialysis Patients JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Winkelmayer, W. C., Liu, J., Brookhart, M. A. 2009; 301 (5): 508-512

    Abstract

    Patients undergoing dialysis at higher altitude receive lower erythropoietin doses, yet achieve higher hemoglobin concentrations. Increased iron availability caused by activation of hypoxia-induced factors at higher altitude may explain this finding. Hypoxia-induced factors are also involved in other pathways that may affect morbidity and mortality.To study whether mortality differed by altitude in patients initiating dialysis.Retrospective cohort of patients initiating dialysis in the United States between 1995 and 2004. Patients were stratified by the average elevation of their residential zip code. Covariates included age, sex, race, Medicaid coverage, dialysis modality, comorbidities, and reported laboratory measurements. We constructed proportional hazards models of all-cause mortality, stratifying by year, and censoring patients at 5 years from first dialysis, at the end of the database (December 31, 2004), or loss to follow-up. We also compared age- and sex-adjusted standardized mortality rates of US patients receiving dialysis with the general population.Mortality from any cause.A total of 804 812 patients initiated dialysis and were followed up for a median of 1.78 years. Crude mortality rates per 1000 person-years were 220.1 at an altitude lower than 76 m (<250 ft), 221.2 from 76 through 609 m (250-1999 ft), 214.6 from 610 through 1218 m (2000-3999 ft), 184.9 from 1219 through 1828 m (4000 to 5999 ft), and 177.2 at an altitude higher than 1828 m (>6000 ft). After multivariable adjustment, compared with patients living at an altitude of lower than 76 m, the relative mortality rates were 0.97 (95% confidence interval [CI], 0.96-0.98) for those living from 76 through 609 m; 0.93 (95% CI, 0.91-0.95), from 610 through 1218 m; 0.88 (95% CI, 0.84-0.91), from 1219 through 1828 m, and 0.85 (95% CI, 0.79-0.92) higher than 1828 m. Age- and sex-standardized mortality decreased more with altitude in patients receiving dialysis than in the general population.Altitude was inversely associated with all-cause mortality among US patients receiving dialysis.

    View details for Web of Science ID 000262992400020

    View details for PubMedID 19190315

  • Comparison of Medicare Claims Versus Physician Adjudication for Identifying Stroke Outcomes in the Women's Health Initiative. Stroke; a journal of cerebral circulation Lakshminarayan, K., Larson, J. C., Virnig, B., Fuller, C., Allen, N. B., Limacher, M., Winkelmayer, W. C., Safford, M. M., Burwen, D. R. 2014; 45 (3): 815-821

    Abstract

    Many studies use medical record review for ascertaining outcomes. One large, longitudinal study, the Women's Health Initiative (WHI), ascertains strokes using participant self-report and subsequent physician review of medical records. This is resource-intensive. Herein, we assess whether Medicare data can reliably assess stroke events in the WHI.Subjects were WHI participants with fee-for-service Medicare. Four stroke definitions were created for Medicare data using discharge diagnoses in hospitalization claims: definition 1, stroke codes in any position; definition 2, primary position stroke codes; and definitions 3 and 4, hemorrhagic and ischemic stroke codes, respectively. WHI data were randomly split into training (50%) and test sets. A concordance matrix was used to examine the agreement between WHI and Medicare stroke diagnosis. A WHI stroke and a Medicare stroke were considered a match if they occurred within ±7 days of each other. Refined analyses excluded Medicare events when medical records were unavailable for comparison.Training data consisted of 24 428 randomly selected participants. There were 577 WHI strokes and 557 Medicare strokes using definition 1. Of these, 478 were a match. With regard to algorithm performance, specificity was 99.7%, negative predictive value was 99.7%, sensitivity was 82.8%, positive predictive value was 85.8%, and ?=0.84. Performance was similar for test data. Whereas specificity and negative predictive value exceeded 99%, sensitivity ranged from 75% to 88% and positive predictive value ranged from 80% to 90% across stroke definitions.Medicare data seem useful for population-based stroke research; however, performance characteristics depend on the definition selected.

    View details for DOI 10.1161/STROKEAHA.113.003408

    View details for PubMedID 24525955

  • Near-Term Prediction of Sudden Cardiac Death in Older Hemodialysis Patients Using Electronic Health Records CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Goldstein, B. A., Chang, T. I., Mitani, A. A., Assimes, T. L., Winkelmayer, W. C. 2014; 9 (1): 82-91

    Abstract

    Sudden cardiac death is the most common cause of death among individuals undergoing hemodialysis. The epidemiology of sudden cardiac death has been well studied, and efforts are shifting to risk assessment. This study aimed to test whether assessment of acute changes during hemodialysis that are captured in electronic health records improved risk assessment.Data were collected from all hemodialysis sessions of patients 66 years and older receiving hemodialysis from a large national dialysis provider between 2004 and 2008. The primary outcome of interest was sudden cardiac death the day of or day after a dialysis session. This study used data from 2004 to 2006 as the training set and data from 2007 to 2008 as the validation set. The machine learning algorithm, Random Forests, was used to derive the prediction model.In 22 million sessions, 898 people between 2004 and 2006 and 826 people between 2007 and 2008 died on the day of or day after a dialysis session that was serving as a training or test data session, respectively. A reasonably strong predictor was derived using just predialysis information (concordance statistic=0.782), which showed modest but significant improvement after inclusion of postdialysis information (concordance statistic=0.799, P<0.001). However, risk prediction decreased the farther out that it was forecasted (up to 1 year), and postdialytic information became less important.Subtle changes in the experience of hemodialysis aid in the assessment of sudden cardiac death and are captured by modern electronic health records. The collected data are better for the assessment of near-term risk as opposed to longer-term risk.

    View details for DOI 10.2215/CJN.03050313

    View details for Web of Science ID 000329364700013

    View details for PubMedID 24178968

  • Addressing Missing Data in Clinical Studies of Kidney Diseases. Clinical journal of the American Society of Nephrology : CJASN Montez-Rath, M. E., Winkelmayer, W. C., Desai, M. 2014

    Abstract

    Missing data constitute a problem present in all studies of medical research. The most common approach to handling missing data-complete case analysis-relies on assumptions about missing data that rarely hold in practice. The implications of this approach are biased and inefficient descriptions of relationships of interest. Here, various approaches for handling missing data in clinical studies are described. In particular, this work promotes the use of multiple imputation methods that rely on assumptions about missingness that are more flexible than those assumptions relied on by the most common method in use. Furthermore, multiple imputation methods are becoming increasingly more accessible in mainstream statistical software packages, making them both a sound and practical choice. The use of multiple imputation methods is illustrated with examples pertinent to kidney research, and concrete guidance on their use is provided.

    View details for DOI 10.2215/CJN.10141013

    View details for PubMedID 24509298

  • Use of Medicare Data to Identify Coronary Heart Disease Outcomes in the Women's Health Initiative. Circulation. Cardiovascular quality and outcomes Hlatky, M. A., Ray, R. M., Burwen, D. R., Margolis, K. L., Johnson, K. C., Kucharska-Newton, A., Manson, J. E., Robinson, J. G., Safford, M. M., Allison, M., Assimes, T. L., Bavry, A. A., Berger, J., Cooper-DeHoff, R. M., Heckbert, S. R., Li, W., Liu, S., Martin, L. W., Perez, M. V., Tindle, H. A., Winkelmayer, W. C., Stefanick, M. L. 2014; 7 (1): 157-162

    Abstract

    . Unique identifier: NCT00000611.

    View details for DOI 10.1161/CIRCOUTCOMES.113.000373

    View details for PubMedID 24399330

  • Thematic Synthesis of Qualitative Studies on Patient and Caregiver Perspectives on End-of-Life Care in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation Tong, A., Cheung, K. L., Nair, S. S., Kurella Tamura, M., Craig, J. C., Winkelmayer, W. C. 2014

    Abstract

    Although dialysis prolongs life for patients with end-stage kidney disease, 20% of deaths in this population are preceded by dialysis therapy withdrawal. Recently, there has been more focus on conservative (nondialytic) care as a legitimate option, particularly for elderly patients. This study aims to describe patients' and caregivers' perspectives on conservative treatment and end-of-life care in chronic kidney disease (CKD).Systematic review and thematic synthesis of qualitative studies.Patients with CKD and caregivers.MEDLINE, Embase, PsycINFO, CINAHL, and reference lists were searched to May 2013.Thematic synthesis was used to analyze the findings.26 studies involving more than 711 patients (non-dialysis dependent [n=41], hemodialysis [n=544], peritoneal dialysis [n=9]; unspecified dialysis modality [n=31], conservative management [n=86]) and 178 caregivers were included. We identified 5 themes: invasive suffering (bodily deterioration, loss of freedom and independence, unyielding fatigue and pain, resignation, treatment burden and harm, financial strain), personal vulnerability (imminence of death, misunderstanding and judgment, autonomy and dignity, medical abandonment, trust and safety), relational responsibility (being a burden, demonstrating loyalty, protecting others from grief), negotiating existential tensions (accepting natural course of life, disrupted aging, worthlessness, living on borrowed time, respecting sanctity of life, life satisfaction, preserving self-identity), and preparedness (decisional clarity, informational power, spirituality and hope).Non-English articles were excluded; therefore, the transferability of findings to other populations is unclear.Some patients with CKD experience physical and psychosocial frailty and feel ambivalent about prolonging life. Some caregivers believe in providing relief from suffering, but are uncertain about making decisions regarding dialysis therapy initiation and discontinuation. We suggest that CKD management should encompass palliative care strategies that promote emotional resilience, sense of well-being, and self-value. Also, respectful and attentive communication may empower patients to convey their values and preferences about their own care.

    View details for DOI 10.1053/j.ajkd.2013.11.017

    View details for PubMedID 24411716

  • Cardiovascular disease: Still unresolved: warfarin in ESRD with atrial fibrillation. Nature reviews. Nephrology Winkelmayer, W. C. 2014

    View details for DOI 10.1038/nrneph.2014.48

    View details for PubMedID 24642800

  • State Medicaid Coverage, ESRD Incidence, and Access to Care. Journal of the American Society of Nephrology : JASN Kurella-Tamura, M., Goldstein, B. A., Hall, Y. N., Mitani, A. A., Winkelmayer, W. C. 2014

    Abstract

    The proportion of low-income nonelderly adults covered by Medicaid varies widely by state. We sought to determine whether broader state Medicaid coverage, defined as the proportion of each state's low-income nonelderly adult population covered by Medicaid, associates with lower state-level incidence of ESRD and greater access to care. The main outcomes were incidence of ESRD and five indicators of access to care. We identified 408,535 adults aged 20-64 years, who developed ESRD between January 1, 2001, and December 31, 2008. Medicaid coverage among low-income nonelderly adults ranged from 12.2% to 66.0% (median 32.5%). For each additional 10% of the low-income nonelderly population covered by Medicaid, there was a 1.8% (95% confidence interval, 1.0% to 2.6%) decrease in ESRD incidence. Among nonelderly adults with ESRD, gaps in access to care between those with private insurance and those with Medicaid were narrower in states with broader coverage. For a 50-year-old white woman, the access gap to the kidney transplant waiting list between Medicaid and private insurance decreased by 7.7 percentage points in high (>45%) versus low (<25%) Medicaid coverage states. Similarly, the access gap to transplantation decreased by 4.0 percentage points and the access gap to peritoneal dialysis decreased by 3.8 percentage points in high Medicaid coverage states. In conclusion, states with broader Medicaid coverage had a lower incidence of ESRD and smaller insurance-related access gaps.

    View details for DOI 10.1681/ASN.2013060658

    View details for PubMedID 24652791

  • IV iron dosing regimens: choice of agent and dosing frequency. Nephrology news & issues Winkelmayer, W. C. 2014; 28 (2): 10-1, 18

    View details for PubMedID 24649746

  • Prognostic Stratification in Older Adults Commencing Dialysis. The journals of gerontology. Series A, Biological sciences and medical sciences Cheung, K. L., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C., Periyakoil, V. S., Kurella Tamura, M. 2014

    Abstract

    Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice.In a cohort of patients aged ?67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic.Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ?9 or an hospice eligibility criteria ?3 had relatively high specificity.Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.

    View details for DOI 10.1093/gerona/glt289

    View details for PubMedID 24482541

  • Differences in Access to Kidney Transplantation between Hispanic and Non-Hispanic Whites by Geographic Location in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Arce, C. M., Goldstein, B. A., Mitani, A. A., Lenihan, C. R., Winkelmayer, W. C. 2013; 8 (12): 2149-2157

    Abstract

    Hispanic patients undergoing chronic dialysis are less likely to receive a kidney transplant compared with non-Hispanic whites. This study sought to elucidate disparities in the path to receipt of a deceased donor transplant between Hispanic and non-Hispanic whites.Using the US Renal Data System, 417,801 Caucasians who initiated dialysis between January 1, 1995 and December 31, 2007 with follow-up through 2008 were identified. This study investigated time from first dialysis to first kidney transplantation, time from first dialysis to waitlisting, and time from waitlisting to kidney transplantation. Multivariable Cox regression estimated cause-specific hazard ratios (HRCS) and subdistribution (competing risk) hazard ratios (HRSD) for Hispanics versus non-Hispanic whites.Hispanics experienced lower adjusted rates of deceased donor kidney transplantation than non-Hispanic whites (HRCS, 0.77; 95% confidence interval [95% CI], 0.75 to 0.80) measured from dialysis initiation. No meaningful differences were found in time from dialysis initiation to placement on the transplant waitlist. Once waitlisted, Hispanics had lower adjusted rates of deceased donor kidney transplantation (HRCS, 0.66; 95% CI, 0.64 to 0.68), and the association attenuated once accounting for competing risks (HRSD, 0.79; 95% CI, 0.77 to 0.81). Additionally controlling for blood type and organ procurement organization further reduced the disparity (HRSD, 0.99; 95% CI, 0.96 to 1.02).After accounting for geographic location and controlling for competing risks (e.g., Hispanic survival advantage), the disparity in access to deceased donor transplantation was markedly attenuated among Hispanics compared with non-Hispanic whites. To overcome the geographic disparities that Hispanics encounter in the path to transplantation, organ allocation policy revisions are needed to improve donor organ equity.

    View details for DOI 10.2215/CJN.01560213

    View details for Web of Science ID 000327951100017

    View details for PubMedID 24115195

  • Strategies for Postmarketing Surveillance of Drugs and Devices in Patients with ESRD Undergoing Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vardi, M., Yeh, R. W., Herzog, C. A., Winkelmayer, W. C., Setoguchi, S., Charytan, D. M. 2013; 8 (12): 2213-2220

    Abstract

    The lack of evidence on the effectiveness and safety of interventions in chronic dialysis patients has been a subject of continuing criticism. New technologies are often introduced into the market without having specifically studied or even included patients with advanced kidney disease. Therefore, the need to generate valid effectiveness and safety data in this vulnerable subpopulation is of utmost importance. The US Food and Drug Administration has recently placed an increased focus on safety surveillance, and sponsors must now meet this additional postmarketing commitment. In patients with ESRD, the unique data collection environment in the United States allows for creative and efficient study designs to meet the needs of patients, providers, and sponsors. The purpose of this manuscript is to review the methodological and practical aspects of the different options for postmarketing study design in this field, with critical appraisal of their advantages and disadvantages.

    View details for DOI 10.2215/CJN.05130513

    View details for Web of Science ID 000327951100025

    View details for PubMedID 23970129

  • Commentary on 'The DOPPS Practice Monitor for US Dialysis Care: Update on Trends in Anemia Management 2 Years Into the Bundle': Iron(y) Abounds 2 Years Later. American journal of kidney diseases Weiner, D. E., Winkelmayer, W. C. 2013; 62 (6): 1217-1220

    View details for DOI 10.1053/j.ajkd.2013.10.006

    View details for PubMedID 24267389

  • Multivessel coronary revascularization and outcomes in kidney transplant recipients. Transplant international Lenihan, C. R., Montez-Rath, M. E., Winkelmayer, W. C., Chang, T. I. 2013; 26 (11): 1080-1087

    Abstract

    Coronary artery disease is a major cause of morbidity and mortality in the kidney transplant population. We compared the long-term outcomes of coronary artery bypass graft (CABG) surgery with percutaneous coronary intervention (PCI) for multivessel coronary disease in a contemporary cohort of US kidney transplant recipients. From the U.S. Renal Data System, we identified all adult kidney transplant patients with ?6 months of Medicare A+B undergoing first recorded multivessel coronary revascularization from 1997 to 2009. The associations of CABG versus PCI with death and the composite of death or myocardial infarction (MI) were compared using proportional hazards regression. Of the 2272 patients included in the study, 1594 underwent CABG and 678 underwent PCI. The estimated 5-year survival rate was 55% [95% confidence interval (CI) 53% to 57%] following coronary revascularization, with no significant association between revascularization type and death [adjusted hazard ratio (aHR) = 1.08; CI 0.94-1.23] or the composite of death or MI (aHR = 1.07; CI 0.96-1.18). Separate propensity score-matched analyses yielded similar results. In this analysis of kidney transplant recipients undergoing multivessel coronary revascularization, we found no difference between CABG and PCI in terms of survival or the composite of death and MI.

    View details for DOI 10.1111/tri.12168

    View details for PubMedID 23957580

  • Intravenous Iron Supplementation Practices and Short-Term Risk of Cardiovascular Events in Hemodialysis Patients PLOS ONE Kshirsagar, A. V., Freburger, J. K., Ellis, A. R., Wang, L., Winkelmayer, W. C., Brookhart, M. A. 2013; 8 (11)

    Abstract

    Intravenous iron supplementation is widespread in the hemodialysis population, but there is uncertainty about the safest dosing strategy. We compared the safety of different intravenous iron dosing practices on the risk of adverse cardiovascular outcomes in a large population of hemodialysis patients.A retrospective cohort was created from the clinical database of a large dialysis provider (years 2004-2008) merged with administrative data from the United States Renal Data System. Dosing comparisons were (1) bolus (consecutive doses ? 100 mg exceeding 600 mg during one month) versus maintenance (all other iron doses during the month); and (2) high (> 200 mg over 1 month) versus low dose (? 200 mg over 1 month). We established a 6-month baseline period (to identify potential confounders and effect modifiers), a one-month iron exposure period, and a three-month follow-up period. Outcomes were myocardial infarction, stroke, and death from cardiovascular disease.117,050 patients contributed 776,203 unique iron exposure/follow-up periods. After adjustment, we found no significant associations of bolus dose versus maintenance, hazards ratio for composite outcome, 1.03 (95% C.I. 0.99, 1.07), or high dose versus low dose intravenous iron, hazards ratio for composite outcome, 0.99 (95% C.I. 0.96, 1.03). There were no consistent associations of either high or bolus dose versus low or maintenance respectively among pre-specified subgroups.Strategies favoring large doses of intravenous iron were not associated with increased short-term cardiovascular morbidity and mortality. Investigation of the long-term safety of the various intravenous iron supplementation strategies may still be warranted.

    View details for DOI 10.1371/journal.pone.0078930

    View details for Web of Science ID 000326499300043

    View details for PubMedID 24223866

  • Trends in Relative Mortality Between Hispanic and Non-Hispanic Whites Initiating Dialysis: A Retrospective Study of the US Renal Data System. American journal of kidney diseases Arce, C. M., Goldstein, B. A., Mitani, A. A., Winkelmayer, W. C. 2013; 62 (2): 312-321

    Abstract

    BACKGROUND: Hispanic patients undergoing long-term dialysis experience better survival compared with non-Hispanic whites. It is unknown whether this association differs by age, has changed over time, or is due to differential access to kidney transplantation. STUDY DESIGN: National retrospective cohort study. SETTING & PARTICIPANTS: Using the US Renal Data System, we identified 615,618 white patients 18 years or older who initiated dialysis therapy between January 1, 1995, and December 31, 2007. PREDICTORS: Hispanic ethnicity (vs non-Hispanic whites), year of end-stage renal disease incidence, age (as potential effect modifier). OUTCOMES: All-cause and cause-specific mortality. RESULTS: We found that Hispanics initiating dialysis therapy experienced lower mortality, but age modified this association (P < 0.001). Compared with non-Hispanic whites, mortality in Hispanics was 33% lower at ages 18-39 years (adjusted cause-specific HR [HRcs], 0.67; 95% CI, 0.64-0.71) and 40-59 years (HRcs, 0.67; 95% CI, 0.66-0.68), 19% lower at ages 60-79 years (HRcs, 0.81; 95% CI, 0.80-0.82), and 6% lower at 80 years or older (HRcs, 0.94; 95% CI, 0.91-0.97). Accounting for the differential rates of kidney transplantation, the associations were attenuated markedly in the younger age strata; the survival benefit for Hispanics was reduced from 33% to 10% at ages 18-39 years (adjusted subdistribution-specific HR [HRsd], 0.90; 95% CI, 0.85-0.94) and from 33% to 19% among those aged 40-59 years (HRsd, 0.81; 95% CI, 0.80-0.83). LIMITATIONS: Inability to analyze Hispanic subgroups that may experience heterogeneous mortality outcomes. CONCLUSIONS: Overall, Hispanics experienced lower mortality, but differential access to kidney transplantation was responsible for much of the apparent survival benefit noted in younger Hispanics.

    View details for DOI 10.1053/j.ajkd.2013.02.375

    View details for PubMedID 23647836

  • Temporal Trends in the Incidence, Treatment, and Outcomes of Hip Fracture in Older Patients Initiating Dialysis in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Nair, S. S., Mitani, A. A., Goldstein, B. A., Chertow, G. M., Lowenberg, D. W., Winkelmayer, W. C. 2013; 8 (8): 1336-1342

    Abstract

    BACKGROUND AND OBJECTIVES: Patients with ESRD experience a fivefold higher incidence of hip fracture than the age- and sex-matched general population. Despite multiple changes in the treatment of CKD mineral bone disorder, little is known about long-term trends in hip fracture incidence, treatment patterns, and outcomes in patients on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fourteen annual cohorts (1996-2009) of older patients (?67 years) initiating dialysis in the United States were studied. Eligible patients had Medicare fee-for-service coverage for ?2 years before dialysis initiation and were followed for ?3 years for a first hip fracture. Type of treatment (internal fixation or partial or total hip replacement) was ascertained along with 30-day mortality. Cox and modified Poisson regressions were used to describe trends in study outcomes. RESULTS: This study followed 409,040 patients over 607,059 person-years, during which time 17,887 hip fracture events were recorded (29.3 events/1000 person-years). Compared with patients incident for ESRD in 1996, adjusted hip fracture rates increased until the 2004 cohort (+41%) and declined thereafter. Surgical treatment included internal fixation in 56%, partial hip replacement in 29%, and total hip replacement in 2%, which remained essentially unchanged over time; 30-day mortality after hip fracture declined from 20% (1996) to 16% (2009). CONCLUSIONS: Hip fracture incidence rates remain higher today than in patients reaching ESRD in 1996, despite multiple purported improvements in the management of CKD mineral bone disorder. Although recent declines in incidence and steady declines in associated short-term mortality are encouraging, hip fractures remain among the most common and consequential noncardiovascular complications of ESRD.

    View details for DOI 10.2215/CJN.10901012

    View details for Web of Science ID 000323122500011

    View details for PubMedID 23660182

  • Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients. Transplantation Riegersperger, M., Plischke, M., Steiner, S., Seidinger, D., Sengoelge, G., Winkelmayer, W. C., Sunder-Plassmann, G. 2013; 95 (11): 1338-1345

    Abstract

    Endothelial progenitor cell (EPC) counts are proposed surrogate markers for vascular function and cardiovascular risk. The effect of tacrolimus (TAC) on EPC is unknown.In this randomized controlled trial, we assigned 148 stable long-term kidney transplant recipients (KTR) to maintaining ciclosporin (CSA) or to commencing TAC-based immunosuppression at a 2:1 ratio. EPC counts (CD34/KDR) after 24 months were defined as primary endpoint.The intent-to-treat analysis included 141 KTR (estimated glomerular filtration rate, 46.7 [40.1-61.8] mL/min per 1.73 m). Median (interquartile range [IQR]) EPC counts at baseline and month 24 were 6 (2-9) and 3 (1-9) cells and 4 (2-8) and 2 (0-5) cells per 5×10 mononuclear cells in CSA and TAC, respectively. Median (IQR) circulating angiogenic cells at baseline and month 24 were 28 (10.7-57) and 44.33 (14.6-59.8) cells and 22 (10.8-41) and 21 (9.7-49.5) cells per high-power field in CSA and TAC, respectively. Median (IQR) endothelial cell colony-forming units count per well at baseline and month 24 were 10.5 (3.3-34.3) and 4.38 (1.7-26.5) in CSA and significantly declined from 9.31 (1.8-29.3) to 4.13 (1.1-9.5) in TAC (P=0.003). There were no cardiovascular events in either group.Although late conversion from CSA to TAC appears safe in KTR, conversion to TAC has no favorable effect on EPC. Low EPC levels are associated with a higher risk of subsequent cardiovascular events and are therefore of prognostic value. Their trend to decline over time deserves further examination.

    View details for DOI 10.1097/TP.0b013e31828fabb3

    View details for PubMedID 23594858

  • Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation. American journal of transplantation Lenihan, C. R., Montez-Rath, M. E., Scandling, J. D., Turakhia, M. P., Winkelmayer, W. C. 2013; 13 (6): 1566-1575

    Abstract

    Little is known about the prevalence and outcomes of patients with atrial fibrillation/flutter (AF) who receive a kidney transplant. We identified all patients who had >1 year of uninterrupted Medicare A+B coverage before receiving their first kidney transplant (1997-2009). The presence of pretransplant AF was ascertained from diagnosis codes in Medicare physician claims. We studied the posttransplant outcomes of death, all-cause graft failure, death-censored graft failure and stroke using multivariable Cox regression. Of 62 706 eligible first kidney transplant recipients studied, 3794 (6.4%) were diagnosed with AF prior to kidney transplant. Over a mean follow up of 4.9 years, 40.6% of AF patients and 24.9% without AF died. All-cause and death-censored graft failure were 46.8% and 16.5%, respectively, in the AF group and 36.4% and 19.5%, respectively, in those without AF. Ischemic stroke occurred in 2.8% of patients with and 1.6% of patients without AF. In patients with AF, multivariable-adjusted hazard ratios (95% confidence intervals) for death, graft failure, death-censored graft failure and ischemic stroke were 1.46 (1.38-1.54), 1.41 (1.34-1.48), 1.26 (1.15-1.37) and 1.36 (1.10-1.68), respectively. Pre-existing AF is associated with poor posttransplant outcomes. Special attention should be paid to AF in pretransplant evaluation, counseling and risk stratification of kidney transplant candidates.

    View details for DOI 10.1111/ajt.12197

    View details for PubMedID 23721555

  • Use and safety of heparin-free maintenance hemodialysis in the USA NEPHROLOGY DIALYSIS TRANSPLANTATION Shen, J. I., Mitani, A. A., Chang, T. I., Winkelmayer, W. C. 2013; 28 (6): 1589-1602

    Abstract

    BACKGROUND: Although heparin is used to anticoagulate the extracorporeal circuit for most patients on maintenance hemodialysis (HD), some patients undergo heparin-free HD. We describe the determinants of heparin-free HD and its association with adverse outcomes using data from a national dialysis provider merged with Medicare claims. METHODS: We identified patients aged ?67 years with no recent history of warfarin use who initiated maintenance HD from 2007 to 2008. We applied the Cox regression to a propensity score-matched cohort to estimate the hazards of all-cause mortality, bleeding (gastrointestinal hemorrhage, hemorrhagic stroke, other hemorrhage), atherothrombosis (ischemic stroke, myocardial infarction) and venous thromboembolism (VTE) (deep vein thrombosis, pulmonary embolism). RESULTS: Among 12 468 patients, 836 (6.7%) were dialyzed heparin-free. In multivariable-adjusted analyses, a history of gastrointestinal bleeding, hemorrhagic stroke and lower hemoglobin and platelet counts were associated with higher odds of heparin-free HD. Heparin-free HD use also varied as much as 4-fold by facility region. We found no significant association of heparin-free HD with all-cause mortality [hazard ratio (HR) 1.08; 95% confidence interval (CI): 0.94-1.26], bleeding (HR 1.15; 95% CI: 0.83-1.60), atherothrombosis (HR 1.09, 95% CI: 0.90-1.31) or VTE (HR 1.23, 95% CI: 0.93-1.64) compared with HD with heparin. CONCLUSIONS: Patient markers of increased risk of bleeding and facility region associated with heparin-free HD use. Despite the potential benefits of avoiding heparin use, heparin-free HD was not significantly associated with decreased hazards of death, bleeding or thrombosis, suggesting that it may be no safer than HD with heparin.

    View details for DOI 10.1093/ndt/gft067

    View details for Web of Science ID 000321057700040

    View details for PubMedID 23563280

  • Variation in Nephrologist Visits to Patients on Hemodialysis across Dialysis Facilities and Geographic Locations. Clinical journal of the American Society of Nephrology Erickson, K. F., Tan, K. B., Winkelmayer, W. C., Chertow, G. M., Bhattacharya, J. 2013; 8 (6): 987-994

    Abstract

    BACKGROUND AND OBJECTIVES: Geographic and other variations in medical practices lead to differences in medical costs, often without a clear link to health outcomes. This work examined variation in the frequency of physician visits to patients receiving hemodialysis to measure the relative importance of provider practice patterns (including those patterns linked to geographic region) and patient health in determining visit frequency. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This work analyzed a nationally representative 2006 database of patients receiving hemodialysis in the United States. A variation decomposition analysis of the relative importance of facility, geographic region, and patient characteristics-including demographics, socioeconomic status, and indicators of health status-in explaining physician visit frequency variation was conducted. Finally, the associations between facility, geographic and patient characteristics, and provider visit frequency were measured using multivariable regression. RESULTS: Patient characteristics accounted for only 0.9% of the total visit frequency variation. Accounting for case-mix differences, patients' hemodialysis facilities explained about 24.9% of visit frequency variation, of which 9.3% was explained by geographic region. Visit frequency was more closely associated with many facility and geographic characteristics than indicators of health status. More recent dialysis initiation and recent hospitalization were associated with decreased visit frequency. CONCLUSIONS: In hemodialysis, provider visit frequency depends more on geography and facility location and characteristics than patients' health status or acuity of illness. The magnitude of variation unrelated to patient health suggests that provider visit frequency practices do not reflect optimal management of patients on dialysis.

    View details for DOI 10.2215/CJN.10171012

    View details for PubMedID 23430207

  • The Comparative Short-term Effectiveness of Iron Dosing and Formulations in US Hemodialysis Patients. American journal of medicine Kshirsagar, A. V., Freburger, J. K., Ellis, A. R., Wang, L., Winkelmayer, W. C., Brookhart, M. A. 2013; 126 (6): 541 e1-541 e14

    Abstract

    Intravenous iron is used widely in hemodialysis, yet there are limited data on the effectiveness of contemporary dosing strategies or formulation type.We conducted a retrospective cohort study using data from the clinical database of a large dialysis provider (years 2004-2008) merged with administrative data from the US Renal Data System to compare the effects of intravenous iron use on anemia management. Dosing comparisons were bolus (consecutive doses ?100 mg exceeding 600 mg during 1 month) versus maintenance (all other iron doses during the month); and high (>200 mg over 1 month) versus low dose (?200 mg over 1 month). Formulation comparison was administration of ferric gluconate versus iron sucrose over 1 month. Outcomes were hemoglobin, epoetin dose, transferrin saturation, and serum ferritin during 6 weeks of follow-up.We identified 117,050 patients for the dosing comparison, and 66,207 patients for the formulation comparison. Bolus dosing was associated with higher average adjusted hemoglobin (+0.23 g/dL; 95% confidence interval [CI], 0.21-0.26), transferrin saturation (+3.31%; 95% CI, 2.99-3.63), serum ferritin (+151 ?g/L; 95% CI, 134.9-168.7), and lower average epoetin dose (-464 units; 95% CI, -583 to -343) compared with maintenance. Similar trends were observed with high-dose iron versus low-dose. Iron sucrose was associated with higher adjusted average hemoglobin (+0.16 g/dL; 95% CI, 0.12-0.19) versus ferric gluconate.Strategies favoring large doses of intravenous iron or iron sucrose lead to improved measures of anemia management. These potential benefits should be weighed against risks, which currently remain incompletely characterized.

    View details for DOI 10.1016/j.amjmed.2012.11.030

    View details for PubMedID 23597800

  • Assessments of Causal Effects-Theoretically Sound, Practically Unattainable, and Clinically Not So Relevant CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Heinze, G. 2013; 8 (4): 520-522

    View details for DOI 10.2215/CJN.02200213

    View details for Web of Science ID 000317023300004

    View details for PubMedID 23520043

  • DETERMINANTS OF PERITONEAL DIALYSIS TECHNIQUE FAILURE IN INCIDENT US PATIENTS PERITONEAL DIALYSIS INTERNATIONAL Shen, J. I., Mitani, A. A., Saxena, A. B., Goldstein, B. A., Winkelmayer, W. C. 2013; 33 (2): 155-166

    Abstract

    Switching from peritoneal dialysis (PD) to hemodialysis (HD) is undesirable, because of complications from temporary vascular access, disruption of daily routine, and higher costs. Little is known about the role that social factors play in technique failure. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: We followed for 3 years a nationally representative cohort of US patients who initiated PD in 1996 - 1997. Technique failure was defined as any switch from PD to HD for 30 days or more. We used Cox regression to examine associations between technique failure and demographic, medical, social, and pre-dialysis factors. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs).We identified an inception cohort of 1587 patients undergoing PD. In multivariate analysis, female sex (HR: 0.78; 95% CI: 0.64 to 0.95) was associated with lower rates of technique failure, and black race [compared with white race (HR: 1.48; 95% CI: 1.20 to 1.82)] and receiving Medicaid (HR: 1.48; 95% CI: 1.17 to 1.86) were associated with higher rates. Compared with patients who worked full-time, those who were retired (HR: 1.49; 95% CI: 1.07 to 2.08) or disabled (HR: 1.38; 95% CI: 1.01 to 1.88) had higher rates of failure. Patients with a systolic blood pressure of 140 - 160 mmHg had a higher rate of failure than did those with a pressure of 120 - 140 mmHg (HR: 1.24; 95% CI: 1.00 to 1.52). Earlier referral to a nephrologist (>3 months before dialysis initiation) and the primary decision-maker for the dialysis modality (physician vs patient vs shared) were not associated with technique failure.This study confirms that several socio-demographic factors are associated with technique failure, emphasizing the potential importance of social and financial support in maintaining PD.

    View details for DOI 10.3747/pdi.2011.00233

    View details for Web of Science ID 000315995000007

    View details for PubMedID 23032086

  • Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 20002004 ARTHRITIS AND RHEUMATISM Feldman, C. H., Hiraki, L. T., Liu, J., Fischer, M. A., Solomon, D. H., Alarcon, G. S., Winkelmayer, W. C., Costenbader, K. H. 2013; 65 (3): 753-763

    Abstract

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) disproportionately affect individuals who are members of racial/ethnic minority groups and individuals of lower socioeconomic status (SES). This study was undertaken to investigate the epidemiology and sociodemographics of SLE and LN in the low-income US Medicaid population.We utilized Medicaid Analytic eXtract data, with billing claims from 47 states and Washington, DC, for 23.9 million individuals ages 18-65 years who were enrolled in Medicaid for >3 months in 2000-2004. Individuals with SLE (?3 visits >30 days apart with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0) and with LN (?2 visits with an ICD-9 code for glomerulonephritis, proteinuria, or renal failure) were identified. We calculated SLE and LN prevalence and incidence, stratified by sociodemographic category, and adjusted for number of American College of Rheumatology (ACR) member rheumatologists in the state and SES using a validated composite of US Census variables.We identified 34,339 individuals with SLE (prevalence 143.7 per 100,000) and 7,388 (21.5%) with LN (prevalence 30.9 per 100,000). SLE prevalence was 6 times higher among women, nearly double in African American compared to white women, and highest in the US South. LN prevalence was higher among all racial/ethnic minority groups compared to whites. The areas with lowest SES had the highest prevalence; areas with the fewest ACR rheumatologists had the lowest prevalence. SLE incidence was 23.2 per 100,000 person-years and LN incidence was 6.9 per 100,000 person-years, with similar sociodemographic trends.In this nationwide Medicaid population, there was sociodemographic variation in SLE and LN prevalence and incidence. Understanding the increased burden of SLE and its complications in this low-income population has implications for resource allocation and access to subspecialty care.

    View details for DOI 10.1002/art.37795

    View details for Web of Science ID 000315452400025

    View details for PubMedID 23203603

  • Trends in the incidence of intestinal perforation in US dialysis patients (1992-2005). Journal of nephrology Yang, J., Lee, T., Montez-Rath, M. E., Desai, M., Winkelmayer, W. C. 2013; 26 (2): 281-288

    Abstract

    Little is known about the incidence of intestinal perforation in patients undergoing dialysis. Concerns exist that sevelamer hydrochloride may increase the risk of intestinal perforation. We examined long-term trends for the incidence of intestinal perforation among US dialysis patients.We studied all dialysis patients (1992-2005) who had Medicare as primary payer. We used ICD-9 diagnosis code 569.83 to ascertain events of intestinal perforation. We studied (a) all perforations and (b) perforations that did not appear to be associated with specific causative conditions (specific diseases or iatrogenic procedures within 7 days of perforation). We used Poisson regression to model the annual number of intestinal perforations and tested for any changes in levels and temporal trends of incidence rates before versus after January 1, 1999.Overall, 1,060,132 patients contributed 2.7 million patient-years. We observed 12,355 events of intestinal perforation and 7,814 spontaneous perforations. The corresponding incidence rates were 4.6 (total) and 2.9 (spontaneous perforation) episodes per 1,000 person-years, respectively. For both outcome definitions, 30-day mortality was 42%. Unadjusted and adjusted incidence rates were not materially different over time. Formal tests for any changes in the level or slope of incidence comparing time periods before and after January 1, 1999, indicated no evidence for any changes in the incidence of intestinal perforation over time.In US dialysis patients, incidence of intestinal perforation was low, but associated with high short-term mortality. We did not detect any significant changes in the incidence of intestinal perforation before versus after approval of sevelamer hydrochloride in late 1998.

    View details for DOI 10.5301/jn.5000104

    View details for PubMedID 22419235

  • More Evidence on an Abominable Pairing Atrial Fibrillation and Kidney Disease CIRCULATION Winkelmayer, W. C. 2013; 127 (5): 560-562
  • Commentary on 'The DOPPS Practice Monitor for US Dialysis Care: Trends Through December 2011': Results From Year One AMERICAN JOURNAL OF KIDNEY DISEASES Weiner, D. E., Winkelmayer, W. C. 2013; 61 (2): 346-348

    View details for DOI 10.1053/j.ajkd.2012.12.003

    View details for Web of Science ID 000313591800024

    View details for PubMedID 23318012

  • Fostering Innovation, Advancing Patient Safety: The Kidney Health Initiative. Clinical journal of the American Society of Nephrology : CJASN Archdeacon, P., Shaffer, R. N., Winkelmayer, W. C., Falk, R. J., Roy-Chaudhury, P. 2013

    Abstract

    To respond to the serious and underrecognized epidemic of kidney disease in the United States, the US Food and Drug Administration and the American Society of Nephrology have founded the Kidney Health Initiative-a public-private partnership designed to create a collaborative environment in which the US Food and Drug Administration and the greater kidney community can interact to optimize the evaluation of drugs, devices, biologics, and food products. The Kidney Health Initiative will bring together all the necessary stakeholders, including patients, regulators, industry, health care providers, academics, and other governmental agencies, to improve patient safety and foster innovation. This initiative is intended to enable the kidney community as a whole to provide the right drug, device, or biologic for administration to the right patient at the right time by fostering partnerships that will facilitate development and delivery of those products and addressing challenges that currently impede these goals.

    View details for PubMedID 23744001

  • Coronary artery bypass graft type and outcomes in maintenance dialysis. The Journal of cardiovascular surgery Shilane, D., Hlatky, M. A., Winkelmayer, W. C., Chang, T. I. 2013

    Abstract

    Aim: Patients with end-stage renal disease (ESRD) on maintenance dialysis have a high burden of coronary disease. Prior studies in non-dialysis patients show better outcomes in coronary artery bypass surgery using the internal mammary artery (IMA) compared with the saphenous vein graft (SVG), but less is known about outcomes in ESRD. We sought to compare the effectiveness of multivessel bypass grafting using IMA versus SVG in patients on maintenance dialysis in the United States. Methods: Cohort study using data from the United States Renal Data System to examine IMA versus SVG in patients on maintenance dialysis undergoing multivessel coronary revascularization. We used Cox proportional hazards regression with multivariable adjustment in the full cohort and in a propensity-score matched cohort. The primary outcome was death from any cause; the secondary outcome was a composite of non-fatal myocardial infarction or death. Results: Overall survival rates were low in this patient population (5-year survival in the matched cohort 25.3%). Use of the IMA compared to SVG was associated with lower risk of death (adjusted hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.84-0.92) and lower risk of the composite outcome (adjusted HR 0.89; CI 0.85-0.93). Results did not materially change in analyses using the propensity-score matched cohort. We found similar results irrespective of patient sex, age, race, or the presence of diabetes, peripheral vascular disease or heart failure. Conclusion: Although overall survival rates were low, IMA was associated with lower risk of mortality and cardiovascular morbidity compared to SVG in patients on dialysis.

    View details for PubMedID 24343371

  • Infection Risk with Bolus versus Maintenance Iron Supplementation in Hemodialysis Patients. Journal of the American Society of Nephrology : JASN Brookhart, M. A., Freburger, J. K., Ellis, A. R., Wang, L., Winkelmayer, W. C., Kshirsagar, A. V. 2013; 24 (7): 1151-8

    Abstract

    Intravenous iron may promote bacterial growth and impair host defense, but the risk of infection associated with iron supplementation is not well defined. We conducted a retrospective cohort study of hemodialysis patients to compare the safety of bolus dosing, which provides a large amount of iron over a short period of time on an as-needed basis, with maintenance dosing, which provides smaller amounts of iron on a regular schedule to maintain iron repletion. Using clinical data from 117,050 patients of a large US dialysis provider merged with data from Medicare's ESRD program, we estimated the effects of iron dosing patterns during repeated 1-month exposure periods on risks of mortality and infection-related hospitalizations during the subsequent 3 months. Of 776,203 exposure/follow-up pairs, 13% involved bolus dosing, 49% involved maintenance dosing, and 38% did not include exposure to iron. Multivariable additive risk models found that patients receiving bolus versus maintenance iron were at increased risk of infection-related hospitalization (risk difference [RD], 25 additional events/1000 patient-years; 95% confidence interval [CI], 16 to 33) during follow-up. Risks were largest among patients with a catheter (RD, 73 events/1000 patient-years; 95% CI, 48 to 99) and a recent infection (RD, 57 events/1000 patient-years; 95% CI, 19 to 99). We also observed an association between bolus dosing and infection-related mortality. Compared with no iron, maintenance dosing did not associate with increased risks for adverse outcomes. These results suggest that maintenance iron supplementation may result in fewer infections than bolus dosing, particularly among patients with a catheter.

    View details for PubMedID 23787911

  • Risk factors of short-term mortality after acute nonvariceal upper gastrointestinal bleeding in patients on dialysis: a population-based study. BMC nephrology Yang, J., Lee, T., Montez-Rath, M. E., Chertow, G. M., Winkelmayer, W. C. 2013; 14: 97-?

    Abstract

    Impaired kidney function is an established predictor of mortality after acute nonvariceal upper gastrointestinal bleeding (ANVUGIB); however, which factors are associated with mortality after ANVUGIB among patients undergoing dialysis is unknown. We examined the associations among demographic characteristics, dialysis-specific features, and comorbid conditions with short-term mortality after ANVUGIB among patients on dialysis.Design: Retrospective cohort study. Setting: United States Renal Data System (USRDS), a nation-wide registry of patients with end-stage renal disease. Participants: All ANVUGIB episodes identified by validated algorithms in Medicare-covered patients between 2003 and 2007. Measurements: Demographic characteristics and comorbid conditions from 1 year of billing claims prior to each bleeding event. We used logistic regression extended with generalized estimating equations methods to model the associations among risk factors and 30-day mortality following ANVUGIB events.From 2003 to 2007, we identified 40,016 eligible patients with 50,497 episodes of ANVUGIB. Overall 30-day mortality was 10.7% (95% CI: 10.4-11.0). Older age, white race, longer dialysis vintage, peritoneal dialysis (vs. hemodialysis), and hospitalized (vs. outpatient) episodes were independently associated with a higher risk of 30-day mortality. Most but not all comorbid conditions were associated with death after ANVUGIB. The joint ability of all factors captured to discriminate mortality was modest (c=0.68).We identified a profile of risk factors for 30-day mortality after ANVUGIB among patients on dialysis that was distinct from what had been reported in non-dialysis populations. Specifically, peritoneal dialysis and more years since initiation of dialysis were independently associated with short-term death after ANVUGIB.

    View details for DOI 10.1186/1471-2369-14-97

    View details for PubMedID 23621917

  • Trends in acute kidney injury, associated use of dialysis, and mortality after cardiac surgery, 1999 to 2008. Annals of thoracic surgery Lenihan, C. R., Montez-Rath, M. E., Mora Mangano, C. T., Chertow, G. M., Winkelmayer, W. C. 2013; 95 (1): 20-28

    Abstract

    The development of acute kidney injury (AKI) after cardiac surgery is associated with significant mortality, morbidity, and cost. The last decade has seen major changes in the complexity of cardiac surgical candidates and in the number and type of cardiac surgical procedures being performed.Using data from the Nationwide Inpatient Sample, we determined the annual rates of AKI, AKI requiring dialysis (AKI-D), and inpatient mortality after cardiac surgery in the United States in the years 1999 through 2008.Inpatient mortality with AKI and AKI-D decreased from 27.9% and 45.9%, respectively, in 1999 to 12.8% and 35.3%, respectively, in 2008. Compared with 1999, the odds of AKI and AKI-D in 2008, adjusted for demographic and clinical factors, were 3.30 (95% confidence interval [CI]: 2.89 to 3.77) and 2.23 (95% CI: 1.78 to 2.80), respectively. Corresponding adjusted odds of death associated with AKI and AKI-D were 0.31 (95% CI: 0.26 to 0.36) and 0.47 (95% CI: 0.34 to 0.65.) Taken together, the attributable risks for death after cardiac surgery associated with AKI and AKI-D increased from 30% and 5%, respectively, in 1999 to 47% and 14%, respectively, in 2008.In sum, despite improvements in individual patient outcomes over the decade 1999 to 2008, the population contribution of AKI and AKI-D to inpatient mortality after surgery increased over the same period.

    View details for DOI 10.1016/j.athoracsur.2012.05.131

    View details for PubMedID 23272825

  • Epidemiologic and Statistical Methods for Comparative Effectiveness Research HEART FAILURE CLINICS Hlatky, M. A., Winkelmayer, W. C., Setoguchi, S. 2013; 9 (1): 29-?

    Abstract

    Observational methods are evolving in response to the widespread availability of data from clinical registries, electronic health records, and administrative databases. These approaches will never eliminate the need for randomized trials, but clearly have a role in evaluating the effect of therapies in unselected populations treated in routine practice.

    View details for DOI 10.1016/j.hfc.2012.09.007

    View details for Web of Science ID 000313137800004

    View details for PubMedID 23168315

  • Preoperative Statin Use and Postoperative Acute Kidney Injury AMERICAN JOURNAL OF MEDICINE Brunelli, S. M., Waikar, S. S., Bateman, B. T., Chang, T. I., Lii, J., Garg, A. X., Winkelmayer, W. C., Choudhry, N. K. 2012; 125 (12): 1195-?

    Abstract

    Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury.We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression.Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery.Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.

    View details for DOI 10.1016/j.amjmed.2012.06.021

    View details for Web of Science ID 000311217600020

    View details for PubMedID 23062398

  • Multivessel Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in ESRD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Shilane, D., Kazi, D. S., Montez-Rath, M. E., Hlatky, M. A., Winkelmayer, W. C. 2012; 23 (12): 2042-2049

    Abstract

    Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.

    View details for DOI 10.1681/ASN.2012060554

    View details for Web of Science ID 000311819000017

    View details for PubMedID 23204445

  • Trends in the Incidence of Atrial Fibrillation in Older Patients Initiating Dialysis in the United States CIRCULATION Goldstein, B. A., Arce, C. M., Hlatky, M. A., Turakhia, M., Setoguchi, S., Winkelmayer, W. C. 2012; 126 (19): 2293-?

    Abstract

    One sixth of US dialysis patients 65 years of age have been diagnosed with atrial fibrillation/flutter (AF). Little is known, however, about the incidence of AF in this population.We identified 258 605 older patients (?67 years of age) with fee-for-service Medicare initiating dialysis in 1995 to 2007, who had not been diagnosed with AF within the previous 2 years. Patients were followed for newly diagnosed AF. Multivariable proportional hazard regression was used to examine temporal trends and associations of race and ethnicity with incident AF. We also studied temporal trends in the mortality and risk of ischemic stroke after new AF. Over 514 395 person-years of follow-up, 76 252 patients experienced incident AF for a crude AF incidence rate of 148/1000 person-years. Incidence of AF increased by 11% (95% confidence interval, 5-16) from 1995 to 2007. Compared with non-Hispanic whites, blacks (-30%), Asians (-19%), Native Americans (-42%), and Hispanics (-29%) all had lower rates of incident AF. Mortality after incident AF decreased by 22% from 1995 to 2008. Even more pronounced reductions were seen for incident ischemic stroke during these years.The incidence of AF is high in older patients initiating dialysis in the United States and has been increasing over the 13 years of study. Mortality declined during that time but remained >50% during the first year after newly diagnosed AF. Because data on warfarin use were not available, we were unable to study whether trends toward better outcomes could be explained by higher rates of oral anticoagulation.

    View details for Web of Science ID 000310744100010

    View details for PubMedID 23032326

  • Predialyis Nephrology Care of Older Individuals Approaching End-Stage Renal Disease SEMINARS IN DIALYSIS Winkelmayer, W. C., Tamura, M. K. 2012; 25 (6): 628-632

    Abstract

    Many older patients with advanced CKD approaching ESRD do not receive timely nephrology care, although data suggest that the situation may be improving. In 2005-2008, 43% of older patients who initiated renal replacement therapy had experienced an outpatient nephrologist consultation more than 1 year before starting treatment. Earlier consultation with a nephrologist has been found to provide better access to peritoneal dialysis and kidney transplantation, better preparation for the chosen dialytic modality, and improved survival after start of dialysis or receipt of a kidney transplant. Recent data suggest that older individuals are less likely to receive treatment for ESRD compared with younger individuals in whom almost all receive dialysis treatment or transplantation. Little is known about the role nephrologists play in the decision whether to initiate dialysis or choose a conservative route among older adults with ESRD. Defining the appropriate role and involvement of nephrologists in the decision about initiating renal replacement therapy in older adults seems ripe for further investigation and discussion.

    View details for DOI 10.1111/sdi.12036

    View details for Web of Science ID 000311404400007

    View details for PubMedID 23173891

  • Anticoagulation for atrial fibrillation in patients on dialysis: are the benefits worth the risks? CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Shen, J. I., Turakhia, M. P., Winkelmayer, W. C. 2012; 21 (6): 600-606

    Abstract

    Atrial fibrillation is common among patients with end-stage renal disease undergoing hemodialysis. Although oral anticoagulation is recommended for stroke prevention in most patients with atrial fibrillation, limited evidence is available to guide treatment in hemodialysis patients with this arrhythmia. We summarize the available evidence on the epidemiology of atrial fibrillation in dialysis patients and review the data on the effectiveness of oral anticoagulation in this population.Atrial fibrillation is increasingly common in patients undergoing chronic hemodialysis, especially among older patients wherein one in six patients is diagnosed with this arrhythmia. Patients with atrial fibrillation experience double the mortality of otherwise similar patients without it. Few hemodialysis patients with atrial fibrillation receive oral anticoagulation, which is consistently associated with excess risks of hemorrhagic stroke. Observational studies did not detect a beneficial association of oral anticoagulation with the risk of ischemic stroke, with some studies describing higher risks of ischemic stroke among warfarin users. New therapeutic options including one oral direct thrombin inhibitor and two oral factor Xa inhibitors have become available, but were not tested in patients with advanced kidney disease.Atrial fibrillation is increasingly common in patients undergoing hemodialysis, yet little is known about the optimal management of these patients. The current evidence does not support net benefits from oral anticoagulation in the dialysis population.

    View details for DOI 10.1097/MNH.0b013e32835856fd

    View details for Web of Science ID 000310061500006

    View details for PubMedID 23079746

  • Saving the Kidneys by Sparing Intravenous Chloride? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Waikar, S. S., Winkelmayer, W. C. 2012; 308 (15): 1583-1585

    View details for Web of Science ID 000309858100026

    View details for PubMedID 23073956

  • Causal or Casual?-The Association Between Consumption of Artificially Sweetened Carbonated Beverages and Vascular Disease JOURNAL OF GENERAL INTERNAL MEDICINE Anand, S., Winkelmayer, W. C. 2012; 27 (9): 1100-1101

    View details for DOI 10.1007/s11606-012-2126-1

    View details for Web of Science ID 000307511300004

    View details for PubMedID 22692638

  • Factors affecting response and tolerability to ferumoxytol in nondialysis chronic kidney disease patients CLINICAL NEPHROLOGY Fishbane, S., Bolton, W. K., Winkelmayer, W. C., Strauss, W., Li, Z., Pereira, B. J. 2012; 78 (3): 181-188

    Abstract

    Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients.A series of post-hoc efficacy and safety analyses were performed using pooled data from two identically designed Phase III studies in 608 nondialysis CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol within 5 ± 3 days versus oral iron.Ferumoxytol resulted in a significant increase in hemoglobin in the presence and absence of ESA, and across a range of baseline hemoglobin, transferrin saturation, ferritin, and reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were similar across quartiles of change in hemoglobin; there were no trends suggesting an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin or faster rate of hemoglobin rise. There was no meaningful difference in the rate of AEs, serious AEs, and cardiovascular AEs between patients receiving or not receiving ESA.These analyses add to the knowledge of predictors of response and safety outcomes associated with i.v. iron therapy in nondialysis CKD patients.

    View details for DOI 10.5414/CN107397

    View details for Web of Science ID 000309378900003

    View details for PubMedID 22874106

  • Use and Safety of Unfractionated Heparin for Anticoagulation During Maintenance Hemodialysis AMERICAN JOURNAL OF KIDNEY DISEASES Shen, J. I., Winkelmayer, W. C. 2012; 60 (3): 473-486

    Abstract

    Anticoagulation is essential to hemodialysis, and unfractionated heparin (UFH) is the most commonly used anticoagulant in the United States. However, there is no universally accepted standard for its administration in long-term hemodialysis. Dosage schedules vary and include weight-based protocols and low-dose protocols for those at high risk of bleeding, as well as regional anticoagulation with heparin and heparin-coated dialyzers. Adjustments are based largely on clinical signs of under- and overanticoagulation. Risks of UFH use include bleeding, heparin-induced thrombocytopenia, hypertriglyceridemia, anaphylaxis, and possibly bone mineral disease, hyperkalemia, and catheter-associated sepsis. Alternative anticoagulants include low-molecular-weight heparin, direct thrombin inhibitors, heparinoids, and citrate. Anticoagulant-free hemodialysis and peritoneal dialysis also are potential substitutes. However, some of these alternative treatments are not as available as or are more costly than UFH, are dependent on country and health care system, and present dosing challenges. When properly monitored, UFH is a relatively safe and economical choice for anticoagulation in long-term hemodialysis for most patients.

    View details for DOI 10.1053/j.ajkd.2012.03.017

    View details for Web of Science ID 000307941200022

    View details for PubMedID 22560830

  • Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US medicaid beneficiary population ARTHRITIS AND RHEUMATISM Hiraki, L. T., Feldman, C. H., Liu, J., Alarcon, G. S., Fischer, M. A., Winkelmayer, W. C., Costenbader, K. H. 2012; 64 (8): 2669-2676

    Abstract

    To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population.Children ages 3 years to <18 years with a diagnosis of SLE (defined as ?3 claims with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ?2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups.Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups.In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and incidence of lupus nephritis in the US to date.

    View details for DOI 10.1002/art.34472

    View details for Web of Science ID 000306906500027

    View details for PubMedID 22847366

  • Commentary on 'The DOPPS Practice Monitor for US Dialysis Care: Trends Through August 2011': An ESA Confluence AMERICAN JOURNAL OF KIDNEY DISEASES Weiner, D. E., Winkelmayer, W. C. 2012; 60 (1): 165-167

    View details for Web of Science ID 000305406200023

    View details for PubMedID 22560743

  • Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, J. P., Desai, M., Chertow, G. M., Winkelmayer, W. C. 2012; 23 (6): 1078-1085

    Abstract

    The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ?67 years who initiated dialysis between July 2005 and December 2008 with ?2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the ? statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ?12 months, accuracy was 70% (?=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.

    View details for DOI 10.1681/ASN.2011080871

    View details for Web of Science ID 000310256300017

    View details for PubMedID 22518002

  • Comparative effectiveness research: what is it and why do we need it in nephrology? NEPHROLOGY DIALYSIS TRANSPLANTATION Chang, T. I., Winkelmayer, W. C. 2012; 27 (6): 2156-2161

    Abstract

    The USA leads other industrialized countries in health care spending but lags behind in terms of health outcomes. There has been growing interest in comparative effectiveness research (CER) as a means to identify best practices to create a more efficient and effective health care system. Two key concepts of CER are that it should (i) compare two or more alternative tests, therapies or procedures and (ii) be conducted in persons, clinical settings and conditions that are representative of the real world. The goal of CER is to provide evidence for clinicians, patients, policy makers and others to make informed decisions that will ultimately improve the overall health of specific subgroups and of the population as a whole. In this narrative review, we first describe the strengths and limitations of various types of studies that constitute CER, including randomized clinical trials, observational studies and systematic reviews, providing examples from the nephrology literature. Because of the concerns regarding confounding in observational CER, we also provide an overview of methods to reduce confounding in these types of studies. Finally, we will discuss why CER pertaining to kidney disease care needs to be a top priority in order to move our field from a largely opinion-based specialty to an evidence-based specialty.

    View details for DOI 10.1093/ndt/gfs154

    View details for Web of Science ID 000304832100008

    View details for PubMedID 22649210

  • Altitude and the risk of cardiovascular events in incident US dialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Winkelmayer, W. C., Hurley, M. P., Liu, J., Brookhart, M. A. 2012; 27 (6): 2411-2417

    Abstract

    Altitude is associated with all-cause mortality in US dialysis patients, but its association with cardiovascular outcomes has not been assessed. We hypothesized that higher altitude would be associated with lower rates of cardiovascular events due to an altered physiological response of dialysis patients to altitude induced hypoxia.We studied 984,265 patients who initiated dialysis from 1995 to 2006. Patients were stratified by the mean elevation of their residential zip codes and were followed from the start of dialysis to the occurrence of several validated cardiovascular endpoints: myocardial infarction, stroke, cardiovascular death and a composite of these end points. Incidence rate ratios across altitude strata were estimated using proportional hazards regression.All outcomes occurred less frequently among patients living at higher altitude compared with patients living at or near sea level, and the association appeared monotonic for all outcomes except for stroke, which was most incident in the 250-1999 ft group. Compared with otherwise similar patients residing at or near sea level, patients living at ? 6000 ft had 31% [95% confidence interval (CI): 21-41%] lower rates of myocardial infarction, 27% (95% CI: 15-37%) lower rates of stroke and 19% (95% CI: 14-24%) lower rates of cardiovascular death. Additional adjustment for biometric information did not materially change these findings. Effect modification between race and altitude was only consistently significant for Native Americans. Altitude did not significantly alter the rates of non-cardiovascular death.We conclude that dialysis patients at higher altitude experience lower rates of cardiovascular events compared to otherwise similar patients at lower altitude.

    View details for DOI 10.1093/ndt/gfr681

    View details for Web of Science ID 000304832100044

    View details for PubMedID 22253068

  • Prevalence of atrial fibrillation and warfarin use in older patients receiving hemodialysis JOURNAL OF NEPHROLOGY Winkelmayer, W. C., Liu, J., Patrick, A. R., Setoguchi, S., Choudhry, N. K. 2012; 25 (3): 341-353

    Abstract

    Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF.We linked US Medicare and prescription claims from older patients undergoing HD in 2 Eastern US states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year, with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past versus absence of warfarin use.Of 6,563 unique patients, 2,185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998 through 2005. Patients aged =85 years and nonwhites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history.While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting its use.

    View details for DOI 10.5301/jn.5000010

    View details for Web of Science ID 000306096600010

    View details for PubMedID 22180223

  • Use of Secondary Prevention Medications among Adults with Reduced Kidney Function CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Gao, L., Brown, T. M., Safford, M. M., Judd, S. E., McClellan, W. M., Limdi, N. A., Muntner, P., Winkelmayer, W. C. 2012; 7 (4): 604-611

    Abstract

    Persons with kidney disease often have cardiovascular disease, but they are less likely to use recommended medications for secondary prevention. The hypothesis was that participants with reduced estimated GFR have lower use of medications recommended for secondary prevention of cardiovascular events (antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, ?-blockers, and statins) and lower medication adherence than participants with preserved estimated GFR.In this cross-sectional analysis, we analyzed data from 6913 participants in the Reasons for Geographic and Racial Differences in Stroke study with a history of cardiovascular disease. Medication use was ascertained by an in-home pill bottle review. Medication adherence was assessed using a validated four-item scale.Among participants with a history of cardiovascular disease, 59.8% used antiplatelet agents, 49.9% used angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 41.6% used ?-blockers, and 53.0% used statins. Compared with the referent group (estimated GFR ?60 ml/min per 1.73 m(2)), participants with estimated GFR <45 ml/min per 1.73 m(2) were more likely to use angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (adjusted prevalence ratio=1.14, 95% confidence interval=1.06-1.23), ?-blockers (adjusted prevalence ratio=1.20, 95% confidence interval=1.09-1.32), and statins (adjusted prevalence ratio=1.10, 95% confidence interval=1.01-1.19). Antiplatelet agent use did not differ by estimated GFR category; 30% of participants reported medication nonadherence across all categories of estimated GFR.Among participants with a history of cardiovascular disease, mild to moderate reductions in estimated GFR were associated with similar and even more frequent use of medications for secondary prevention compared with participants with preserved estimated GFR. Overall medication use and adherence were suboptimal.

    View details for DOI 10.2215/CJN.11441111

    View details for Web of Science ID 000302281900013

    View details for PubMedID 22344513

  • Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yang, J., Lee, T., Montez-Rath, M. E., Paik, J., Chertow, G. M., Desai, M., Winkelmayer, W. C. 2012; 23 (3): 495-506

    Abstract

    Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.

    View details for DOI 10.1681/ASN.2011070658

    View details for Web of Science ID 000301206900017

    View details for PubMedID 22266666

  • The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs PLOS ONE Kesselheim, A. S., Myers, J. A., Solomon, D. H., Winkelmayer, W. C., Levin, R., Avorn, J. 2012; 7 (2)

    Abstract

    The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales.We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain.We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p<0.001 for all)). By contrast, for imatinib, approved uses increased significantly over off-label (0.97 vs. 0.47 patients, p<0.001). Spending on off-label uses was highest for lidocaine patch and modafinil (>75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001).In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy.

    View details for DOI 10.1371/journal.pone.0031894

    View details for Web of Science ID 000302873700116

    View details for PubMedID 22363762

  • Hispanic Ethnicity and Vascular Access Use in Patients Initiating Hemodialysis in the United States CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Arce, C. M., Mitani, A. A., Goldstein, B. A., Winkelmayer, W. C. 2012; 7 (2): 289-296

    Abstract

    Hispanics are the largest minority in the United States (comprising 16.3% of the US population) and have 1.5 times the age-, sex-, and race-adjusted incidence of ESRD compared with non-Hispanics. Poor health care access and low-quality care generally received by Hispanics are well documented. However, little is known regarding dialysis preparation of Hispanic patients with progressive CKD.Using data from Medical Evidence Report form CMS-2728-U3, 321,996 adult patients of white or black race were identified who initiated hemodialysis (HD) between July 1, 2005 and December 31, 2008. The form captures Hispanic ethnicity, vascular access use at first outpatient HD, sociodemographic characteristics, and comorbidities. This study also examined whether use of an arteriovenous fistula (AVF) or graft (AVG) was reported.AVF/AVG use was reported in 14.5% of Hispanics and 17.6% in non-Hispanics (P<0.001). The unadjusted prevalence ratio (PR) was 0.85 (95% confidence interval [95% CI], 0.83-0.88), indicating that Hispanics were 15% less likely to use AVG/AVF for their first outpatient HD. Adjustment for age, sex, and race, as well as a large number of comorbidities and frailty indicators, did not change this association (PR, 0.85; 95% CI, 0.83-0.88). Further adjustment for timing of first predialysis nephrology care, however, attenuated the PR by two-thirds (PR, 0.94; 95% CI, 0.92-0.97).Hispanics are less likely to use arteriovenous access for first outpatient HD compared with non-Hispanics, which seems to be explained by variation in the access to predialysis nephrology care.

    View details for DOI 10.2215/CJN.08370811

    View details for Web of Science ID 000300124300014

    View details for PubMedID 22114148

  • Commentary on 'The DOPPS Practice Monitor for US Dialysis Care: Trends Through April 2011': No Surprises Yet AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Weiner, D. E. 2012; 59 (2): 312-314

    View details for DOI 10.1053/j.ajkd.2011.11.006

    View details for Web of Science ID 000299317500024

    View details for PubMedID 22243946

  • Quantifying the benefit of early living-donor renal transplantation with a simulation model of the Dutch renal replacement therapy population NEPHROLOGY DIALYSIS TRANSPLANTATION Liem, Y. S., Wong, J. B., Winkelmayer, W. C., Weimar, W., Wetzels, J. F., de Charro, F. T., Kaandorp, G. C., Stijnen, T., Hunink, M. G. 2012; 27 (1): 429-434

    Abstract

    Early living-donor transplantation improves patient- and graft-survival compared with possible cadaveric renal transplantation (RTx), but the magnitude of the survival gain is unknown. For patients starting renal replacement therapy (RRT), we aimed to quantify the survival benefit of early living-donor transplantation compared with dialysis and possible cadaveric transplantation and to estimate the population benefit from increasing the early transplantation rate.We used a decision-analytic computer-simulation model, with a lifetime time horizon, simulating patients starting RRT, using data from the Dutch End-Stage Renal Disease Registry and published data. We compared the (quality adjusted) life expectancy (LE) of 'early living-donor RTx' and 'dialysis' (with possible cadaveric RTx if available).LE and quality-adjusted LE benefits of the early living-donor RTx compared with the dialysis strategy for 40-year-old patients ranged from 7.5 to 9.9 life years (LYs) [6.7-8.8 quality-adjusted life years (QALYs)] depending on the primary renal disease. For 70-year-old patients, the benefit was 4.3-6.0 LYs (4.3-6.0 QALYs). Increasing the early transplantation rate from currently 5.8 to 22.2% (the highest in Europe) would increase average LE by 1.2 LYs and total LE for annual incident cases in the Netherlands by >1800 LYs.Efforts to increase early living-donor RTx could potentially substantially increase LE for patients starting RRT, especially in younger patients.

    View details for DOI 10.1093/ndt/gfr294

    View details for Web of Science ID 000299957700064

    View details for PubMedID 21606383

  • What Caused Excess Strokes in Patients Randomized to Darbepoetin in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)? No Smoking Gun CIRCULATION Winkelmayer, W. C. 2011; 124 (25): 2805-2808
  • Impact of Nephrologic Care in the Early Management of Chronic Kidney Disease In reply ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Chertow, G. M., Tamura, M. K. 2011; 171 (22): 2067-2067
  • Variation in initial kidney replacement therapy for end-stage renal disease due to lupus nephritis in the United States ARTHRITIS CARE & RESEARCH Devlin, A., Waikar, S., Solomon, D. H., Lu, B., Shaykevich, T., Alarcon, G. S., Winkelmayer, W. C., Costenbader, K. H. 2011; 63 (12): 1642-1653

    Abstract

    Little is known about the patterns of use of initial kidney replacement therapies among patients with lupus nephritis (LN) end-stage renal disease (ESRD). We aimed to identify sociodemographic and clinical factors associated with variation in initial kidney replacement therapies among LN ESRD patients.Patients with incident LN ESRD (1995-2006) were identified in the US Renal Data System. Age, sex, race, ethnicity, medical insurance, employment status, residential region, clinical factors, and comorbidities were considered as potential predictors of ESRD treatment choice, i.e., peritoneal dialysis (PD), hemodialysis (HD), or preemptive kidney transplantation in age-adjusted and multivariable-adjusted logistic regression analyses.Of the 11,317 individuals with incident LN ESRD, 82.0% initiated HD, 12.2% initiated PD, and 2.8% underwent preemptive kidney transplantation. Receiving initial PD was significantly associated with earlier calendar year, female sex, higher albumin and hemoglobin levels, and lower serum creatinine levels. African Americans (versus whites), Medicaid beneficiaries and those with no health insurance (versus private insurance), and those unemployed (versus employed) had significantly reduced PD initiation. Comorbidities including congestive heart failure, peripheral vascular disease, and the inability to ambulate were also associated with decreased PD. Many sociodemographic and clinical factors favoring PD were associated with preemptive kidney transplant (versus dialysis) as well.Few patients with LN ESRD receive initial PD or preemptive kidney transplantation. Race, ethnicity, employment, and medical insurance type are strongly associated with initial kidney replacement therapy choice. Future studies need to investigate the appropriateness of sociodemographic and clinical variation and the comparative effectiveness of kidney replacement therapies for LN ESRD.

    View details for DOI 10.1002/acr.20607

    View details for Web of Science ID 000297457300002

    View details for PubMedID 22058067

  • Effectiveness and Safety of Warfarin Initiation in Older Hemodialysis Patients with Incident Atrial Fibrillation CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Liu, J., Setoguchi, S., Choudhry, N. K. 2011; 6 (11): 2662-2668

    Abstract

    Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown.We assembled a cohort of older hemodialysis patients who initiated dialysis without prior record of AF and who had prescription drug benefits through three state-administered programs. The index event was a first hospitalization with diagnosed AF; patients with any recorded prior warfarin use were excluded. Eligible patients survived ?30 days from discharge, and new warfarin use was recorded from prescription records during that 30-day window. Propensity-matched warfarin users and nonusers were compared using Cox regression. Outcomes included ischemic stroke, hemorrhagic stroke, and mortality.Among 2313 patients with new AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over 2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke, gastrointestinal hemorrhage, and mortality did not differ between groups. As-treated analyses yielded similar findings, as did analyses restricted to patients with CHADS(2) scores ?2.Although we confirmed association between warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no association between warfarin use and ischemic stroke. Adequately powered randomized trials are required to conclusively determine the risks and benefits of the studied warfarin indication in hemodialysis patients.

    View details for DOI 10.2215/CJN.04550511

    View details for Web of Science ID 000296821300018

    View details for PubMedID 21959598

  • Air Pollution and Coronary Risk in Kidney Transplant Recipients AMERICAN JOURNAL OF KIDNEY DISEASES Laden, F., Winkelmayer, W. C. 2011; 58 (4): 506-507

    View details for DOI 10.1053/j.ajkd.2011.08.002

    View details for Web of Science ID 000295379600004

    View details for PubMedID 21944961

  • Trends in the Use and Outcomes of Implantable Cardioverter-Defibrillators in Patients Undergoing Dialysis in the United States AMERICAN JOURNAL OF KIDNEY DISEASES Charytan, D. M., Patrick, A. R., Liu, J., Setoguchi, S., Herzog, C. A., Brookhart, M. A., Winkelmayer, W. C. 2011; 58 (3): 409-417

    Abstract

    Sudden cardiac death constitutes the leading cause of death in patients receiving dialysis. Little is known about the trends in implantable cardioverter-defibrillator (ICD) use and the outcomes of such device placement.Retrospective cohort study.US long-term dialysis patients who received an ICD in 1994-2006. PREDICTORS, OUTCOMES, & MEASUREMENTS: ICD utilization rates and incident rates of all-cause mortality, device infections, and other device-related procedures were measured. We compared mortality between recipients and otherwise similar patients who did not receive such a device using high-dimensional propensity score matching. We also examined the associations of demographics, dialysis type, baseline comorbid conditions, cardiovascular events at the time of admission, and recent infection with the study outcomes.9,528 patients received an ICD in 1994-2006, with >88% placed after 2000. Almost all ICD use in the 1990s was for secondary prevention, however, half the patients received ICDs for apparent primary prevention in 2006. Mortality rates after implantation were high (448 deaths/1,000 patient-years) and most deaths were cardiovascular. Postimplantation infection rates were high, especially in the first year after implantation (988 events/1,000 patient-years) and were predicted by diabetes and recent infection. Patients receiving ICDs for secondary prevention had an overall 14% (95% CI, 9%-19%) lower mortality risk compared with propensity-matched controls, but these benefits seemed to be restricted to the early postimplantation time.Lack of clinical data, especially for laboratory and heart function studies. Residual confounding by indication.ICD use in dialysis patients is increasing, but rates of all-cause and cardiovascular mortality remain high in dialysis patients receiving these devices. Device infections are common, particularly in patients with recent infections. Randomized trials of ICDs are needed to determine the efficacy, safety, and risk-benefit ratio of these devices in dialysis patients.

    View details for DOI 10.1053/j.ajkd.2011.03.026

    View details for Web of Science ID 000294055100014

    View details for PubMedID 21664735

  • Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis AMERICAN HEART JOURNAL Chang, T. I., Shilane, D., Brunelli, S. M., Cheung, A. K., Chertow, G. M., Winkelmayer, W. C. 2011; 162 (2): 324-330

    Abstract

    Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for patients on dialysis, but there are few data regarding their effectiveness in ESRD.We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization.In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In the propensity score-matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization.In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.

    View details for DOI 10.1016/j.ahj.2011.05.004

    View details for Web of Science ID 000293729400016

    View details for PubMedID 21835294

  • Posttransplantation Anemia: Mechanisms and Management CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yabu, J. M., Winkelmayer, W. C. 2011; 6 (7): 1794-1801

    Abstract

    Treatment of anemia in patients with chronic kidney disease is a topic of increasing interest and controversy. However, anemia in the kidney transplant recipient has received relatively little attention in the literature despite the reported high prevalence of 30% to 40%. The pathogenesis of anemia among kidney transplant recipients is usually multifactorial, including compromised graft function, iron deficiency, immunosuppressive and other medications, and an inflammatory state causing erythropoietin resistance. It is unclear whether posttransplantation anemia is causally linked to cardiovascular events and mortality. Clinicians should screen kidney transplant recipients for posttransplantation anemia and carefully weigh the potential risks and benefits of treatment on an individual basis until well-designed, prospective studies provide further insight. This article reviews the prevalence, pathogenesis, and management of anemia in kidney transplant recipients.

    View details for DOI 10.2215/CJN.01090211

    View details for Web of Science ID 000292618300040

    View details for PubMedID 21734096

  • End-Stage Renal Disease Due to Lupus Nephritis Among Children in the US, 1995-2006 ARTHRITIS AND RHEUMATISM Hiraki, L. T., Lu, B., Alexander, S. R., Shaykevich, T., Alarcon, G. S., Solomon, D. H., Winkelmayer, W. C., Costenbader, K. H. 2011; 63 (7): 1988-1997

    Abstract

    To identify predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality among children with lupus nephritis-associated end-stage renal disease (ESRD).Children ages 5-18 years with new-onset lupus nephritis-associated ESRD were identified in the US Renal Data System (1995-2006). Demographic and clinical characteristics, causes of death, and predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality during the first 5 years of ESRD were investigated. Cox proportional hazards models were used.A total of 583 children had incident lupus nephritis-associated ESRD. The mean ± SD age of the patients at the time of ESRD onset was 16.2 ± 2.4 years; 49% were African American, and 24% were Hispanic. During the 5-year period after the onset of ESRD, 292 (49%) were wait-listed, 193 (33%) received a kidney transplant, and 131 (22%) died. The main causes of death were cardiopulmonary (31%) and infectious (16%). Children living in the northeast and west were more than twice as likely as children in the south to be wait-listed and were >50% more likely than children in the south to undergo transplantation. There were fewer kidney transplants among older versus younger patients (odds ratio [OR] 0.59, P = 0.009), African American versus white patients (OR 0.48, P < 0.001), Hispanic versus non-Hispanic patients (OR 0.63, P = 0.03), and those with Medicaid versus those with private insurance (OR 0.70, P = 0.03). Mortality among African American children was almost double that among white children (OR 1.83, P < 0.001).Among US children with lupus nephritis-associated ESRD, age, race, ethnicity, type of medical insurance, and geographic region were associated with significant variation in 5-year wait-listing for kidney transplantation, kidney transplantation, and mortality.

    View details for DOI 10.1002/art.30350

    View details for Web of Science ID 000292809700027

    View details for PubMedID 21445963

  • Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure JOURNAL OF CARDIAC FAILURE Haddad, F., Fuh, E., Peterson, T., Skhiri, M., Kudelko, K. T., Perez, V. D., Winkelmayer, W. C., Doyle, R. L., Chertow, G. M., Zamanian, R. T. 2011; 17 (7): 533-539

    Abstract

    Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH).We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2).AKI is relatively common in patients with PAH and associated with a short-term risk of death.

    View details for DOI 10.1016/j.cardfail.2011.03.003

    View details for Web of Science ID 000292368500002

    View details for PubMedID 21703524

  • Trends in the Incidence, Demographics, and Outcomes of End-Stage Renal Disease Due to Lupus Nephritis in the US From 1995 to 2006 ARTHRITIS AND RHEUMATISM Costenbader, K. H., Desai, A., Alarcon, G. S., Hiraki, L. T., Shaykevich, T., Brookhart, M. A., Massarotti, E., Lu, B., Solomon, D. H., Winkelmayer, W. C. 2011; 63 (6): 1681-1688

    Abstract

    This study was undertaken to investigate whether recent advances in lupus nephritis treatment have led to changes in the incidence of end-stage renal disease (ESRD) secondary to lupus nephritis, or in the characteristics, treatments, and outcomes of patients with lupus nephritis ESRD.Patients with incident lupus nephritis ESRD (1995-2006) were identified in the US Renal Data System. Trends in sociodemographic and clinical characteristics were assessed. We tested for temporal changes in standardized incidence rates (SIRs) for sociodemographic groups using Poisson regression. Changes in rates of waitlisting for kidney transplant, kidney transplantation, and all-cause mortality were examined using crude and adjusted time-to-event analyses.We identified 12,344 incident cases of lupus nephritis ESRD. Mean age at ESRD onset was 41 years; 81.6% of the patients were women and 49.5% were African American. SIRs for lupus nephritis ESRD among those who were ages 5-39 years, African American, or lived in the southeastern US increased significantly from 1995 to 2006. Increases in body mass index and in the prevalence of both diabetes mellitus and hypertension were detected. Mean serum hemoglobin level at ESRD onset increased, while that of serum creatinine decreased over time. More patients received hemodialysis and fewer received peritoneal dialysis. There was a slight increase in the frequency of preemptive kidney transplantation at ESRD onset, but kidney transplantation rates within the first 3 years of ESRD declined. Mortality did not change over the 12 years of study.Our findings indicate that the characteristics of patients with lupus nephritis ESRD and initial therapies have changed in recent years. While SIRs rose in younger patients, among African Americans, and in the South, outcomes did not improve in over a decade of evaluation.

    View details for DOI 10.1002/art.30293

    View details for Web of Science ID 000291683200027

    View details for PubMedID 21445962

  • Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors: Challenges in Comparative Effectiveness Using Medicare Data CLINICAL PHARMACOLOGY & THERAPEUTICS Setoguchi, S., Shrank, W. H., Liu, J., Lee, J. C., Saya, U., Winkelmayer, W. C., Dreyer, N. A. 2011; 89 (5): 674-682

    Abstract

    An evidence gap exists in comparing the effectiveness of angiotensin receptor II blockers (ARBs) for hypertension with that of angiotensin-converting enzyme inhibitors (ACEIs). We identified elderly hypertensive patients in whom ACEI/ARB therapy had been initiated after hospitalization for coronary artery disease (CAD), heart failure (HF), or stroke and who were eligible for Medicare and state pharmacy assistance programs. Of 18,801 initiators of ACEIs and 2,641 initiators of ARBs, 2,535 died during the follow-up. We observed substantial differences in characteristics between ARB and ACEI initiators, suggesting that ARB users were more health seeking. The incidence of death and sudden cardiac death (SCD) in ACEI initiators was 77 and 22 per 1,000 person-years, respectively. The relative risk for SCD comparing ARB initiators to ACEI initiators was 0.69 (95% confidence interval (CI) 0.50-0.96); when the analysis was restricted to patients with low ejection fraction (EF), the relative risk was 1.1. The reduced risk of SCD can be explained, at least partly, by (i) residual confounding because ARB users were healthier on unobserved domains and (ii) lack of data on EF.

    View details for DOI 10.1038/clpt.2011.17

    View details for Web of Science ID 000289833000015

    View details for PubMedID 21451506

  • The 2011 ESRD Prospective Payment System: An Uncontrolled Experiment AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2011; 57 (4): 542-546

    View details for DOI 10.1053/j.ajkd.2011.01.013

    View details for Web of Science ID 000288657100373

    View details for PubMedID 21333428

  • Kidney Function and Long-Term Medication Adherence after Myocardial Infarction in the Elderly CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Desai, M., Solomon, D. H., Winkelmayer, W. C. 2011; 6 (4): 864-869

    Abstract

    The association of kidney function with long-term outpatient medication adherence in the elderly remains understudied.A cohort of 2103 patients over the age of 65 years enrolled in a pharmacy benefits program after hospital discharge for myocardial infarction was studied. Using linear mixed effects models, the association of baseline kidney function with long-term adherence to recommended medications after myocardial infarction was examined, including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), ?-blockers, and statins. The primary outcome measure was the percentage of days covered as calculated by pharmacy refill data for 12 serial 3-month intervals (totaling 36 months of follow-up).Overall long-term adherence to ACEIs/ARBs, ?-blockers, and statins was poor. The mean percentage of days covered by 36 months was only 50% to 60% for all three medication classes. Patients with baseline kidney dysfunction had significantly lower long-term ACEI/ARB and ?-blocker adherence compared with patients with higher baseline kidney function. Long-term statin adherence did not vary by baseline level of kidney function.Long-term medication adherence after myocardial infarction in the elderly is low, especially in patients with kidney dysfunction. Future strategies to improve medication adherence should pay special attention to the elderly with kidney dysfunction because they may be especially vulnerable to its adverse clinical consequences.

    View details for DOI 10.2215/CJN.07290810

    View details for Web of Science ID 000289223600025

    View details for PubMedID 21233459

  • The Effect of Altitude Change on Anemia Treatment Response in Hemodialysis Patients AMERICAN JOURNAL OF EPIDEMIOLOGY Brookhart, M. A., Bradbury, B. D., Avorn, J., Schneeweiss, S., Winkelmayer, W. C. 2011; 173 (7): 768-777

    Abstract

    Hemodialysis patients who live at high altitude use less exogenous erythropoietin but achieve higher hematocrit levels than those living at a lower altitude. The authors hypothesized that the effect of altitude would be strongest in hemodialysis patients with poor anemia treatment response. To explore this hypothesis, they studied anemia-related outcomes in US hemodialysis patients who move to higher altitudes. Using Medicare and US Geological Survey data, in 1992-2004 they identified instances in which a patient moved from a dialysis center at an altitude of <2,000 feet (600 m) to one at a higher elevation. Of these moves, 5,274 were ?3,000 feet (900 m; the altitude group) and 25,345 were 250-500 feet (75-150 m; the control group). Among patients with poor treatment response at baseline, large increases in hematocrit and decreases in erythropoietin dosing were observed in the altitude relative to the control group. At 6 months, hematocrit had increased more in the altitude group (5.1%, 95% confidence interval (CI): 4.1, 6.2 vs. 3.7%, 95% CI: 3.5, 3.9), and erythropoietin dosing decreased more (4,600 units/week, 95% CI: 500, 8,700 vs. 1,700 units/week, 95% CI: 1,000, 2,400). No effect of altitude was observed in patients with better treatment response at baseline. These results support the hypothesis that altitude-induced hypoxia reduces erythropoietin requirements in hemodialysis patients with treatment-refractory anemia.

    View details for DOI 10.1093/aje/kwq423

    View details for Web of Science ID 000289301200008

    View details for PubMedID 21345929

  • World Kidney Day 2011 JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hostetter, T. H., Kochis, D. J., Shaffer, R. N., Chertow, G., Harmon, W. E., Klotman, P. E., Powe, N. R., Sedor, J. R., Smedberg, P. C., Watnick, S., Winkelmayer, W. C. 2011; 22 (3): 397-398

    View details for DOI 10.1681/ASN.2011020115

    View details for Web of Science ID 000288778800001

    View details for PubMedID 21355055

  • A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease BMC NEPHROLOGY Qunibi, W., Winkelmayer, W. C., Solomon, R., Moustafa, M., Kessler, P., Ho, C., Greenberg, J., Diaz-Buxo, J. A. 2011; 12

    Abstract

    Hyperphosphatemia in patients with chronic kidney disease (CKD) contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD.In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR < 30 mL/min/1.73 m² and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH) levels.At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04). The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p < 0.001) and iPTH was significantly lower in the calcium acetate group compared to placebo (150 ± 157 vs. 351 ± 292 pg/mL respectively; p < 0.001). At 12 weeks, the proportions of subjects who had hypocalcemia were 5.4% and 19.5% for the calcium acetate and the placebo groups, respectively, while the proportions of those with hypercalcemia were 13.5% and 0%, respectively. Adverse events did not differ between the treatment groups.In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period.www.clinicaltrials.gov NCT00211978.

    View details for DOI 10.1186/1471-2369-12-9

    View details for Web of Science ID 000304356700001

    View details for PubMedID 21324193

  • The Increasing Prevalence of Atrial Fibrillation among Hemodialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Patrick, A. R., Liu, J., Brookhart, M. A., Setoguchi, S. 2011; 22 (2): 349-357

    Abstract

    A half million Americans have ESRD, which puts them at high risk for cardiovascular disease and poor outcomes. Little is known about the epidemiology of atrial fibrillation among patients with ESRD. We analyzed data from annual cohorts (1992 to 2006) of prevalent hemodialysis patients from the United States Renal Data System. In each cohort, we searched 1 year of medical claims for relevant diagnosis codes to determine the prevalence of atrial fibrillation. Among 2.5 million patient observations, 7.7% had atrial fibrillation, with the prevalence increasing 3-fold from 3.5% (1992) to 10.7% (2006). The number of affected patients increased from 3620 to 23,893 (6.6-fold) during this period. Older age, male gender, and several comorbid conditions were associated with increased risk for atrial fibrillation. Compared with otherwise similar Caucasians, the prevalence of atrial fibrillation rates was substantially lower for blacks, Asians, and Native Americans. One-year mortality was twice as high among hemodialysis patients with atrial fibrillation compared with those without (39% versus 19%), and this increased risk was constant during the 15 years of the study. In conclusion, the prevalence of diagnosed atrial fibrillation among patients receiving hemodialysis in the United States is increasing, varies by race, and remains associated with substantially increased mortality. Identifying potentially modifiable risk factors for incident atrial fibrillation requires further investigation.

    View details for DOI 10.1681/ASN.2010050459

    View details for Web of Science ID 000287673600021

    View details for PubMedID 21233416

  • Comparative Effectiveness of Calcium-Containing Phosphate Binders in Incident US Dialysis Patients CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Liu, J., Kestenbaum, B. 2011; 6 (1): 175-183

    Abstract

    Few studies have assessed the association between phosphate binder use and hard outcomes in dialysis patients. Furthermore, the comparative effectiveness of calcium carbonate and acetate is untested. We studied the association between use versus nonuse of calcium-containing phosphate binders (CCPBs) and mortality from any cause. We also tested whether mortality differed among users of individual CCPBs.A nationally representative prospective cohort of incident U.S. dialysis patients (1996 to 1997), assembled before the availability of sevelamer and lanthanum, was used. Use of each CCPB was ascertained from chart abstraction records. A large number of sociodemographic, clinical, and laboratory characteristics were available for confounding control in multivariate and propensity score-matched Cox regression models.Among 3603 incident dialysis patients, 77.5% used a CCPB, whereas 22.5% did not. Baseline use of CCPB was associated with an adjusted 19% lower mortality rate among CCPB users compared with nonusers. With successful matching of 800 exposed and nonexposed individuals on their exposure propensity score, however, CCPB users and nonusers had similar mortality. No mortality differences were observed between calcium acetate and calcium carbonate users in crude, adjusted, or propensity-matched analyses.No association was found between CCPB use and 1-year mortality in incident dialysis patients; choice of calcium carbonate versus acetate was also not associated with this outcome. Randomized trials are necessary to understand whether the prevailing practice of phosphate-binding therapy actually reduces adverse clinical outcomes.

    View details for DOI 10.2215/CJN.05060610

    View details for Web of Science ID 000286452900024

    View details for PubMedID 20947790

  • Against TREATing All Patients Alike: Lessons from an FDA Advisory Committee Meeting JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C. 2011; 22 (1): 1-2

    View details for DOI 10.1681/ASN.2010111133

    View details for Web of Science ID 000288046500001

    View details for PubMedID 21164031

  • Guideline-conformity of initiation with oral hypoglycemic treatment for patients with newly therapy-dependent type 2 diabetes mellitus in Austria PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Winkelmayer, W. C., Stedman, M. R., Pogantsch, M., Wieninger, P., Bucsics, A., Asslaber, M., Bauer, R., Burkhardt, T., Schautzer, A., Brookhart, M. A. 2011; 20 (1): 57-65

    Abstract

    To determine guideline conformity of initiation of oral hypoglycemic (OH) treatment for type 2 diabetes in Austria; to study patient and prescriber correlates of recommended initiation with metformin monotherapy.We used claims from 11 sickness funds that covered 7.5 million individuals, representing >90% of the Austrian population. First-time OH use was defined as a first filled prescription after one year without any OH drug or insulin. Among these incident users, we described the OH drug class used and defined correlates of initiation with metformin monotherapy.From 1/2007 to 6/2008, we identified 42,882 incident users of an OH drug: 70.8% used metformin, 24.7% used a sulfonylurea, and 4.5% initiated treatment with another class. We estimated the incidence of OH-dependent type 2 diabetes at 3.8-4.4 per 1000 patient-years. We conducted multivariate analyses among 39 077 patients with available prescriber information. Independent correlates of initiation with metformin were younger age, female gender, waived co-payment, more recent initiation, fewer hospital days and more therapeutic classes received in the year prior to first OH therapy (all p < 0.001). Prescriber specialty and age (p < 0.001), but not gender, were also associated with metformin initiation. Approximately 20% of metformin initiators had a second OH drug added within <18 months. While we were unable to ascertain specific contraindications to metformin (renal insufficiency, hepatic failure), <10% of the general population are expected to have these conditions.Seventy per cent of new initiators of OH treatment in Austria received metformin as recommended by international guidelines. At least 20% did not, taking into account possible contraindications, which provides an opportunity for intervention.

    View details for DOI 10.1002/pds.2059

    View details for Web of Science ID 000286071700008

    View details for PubMedID 21182153

  • The Challenges of Cost-Effectiveness Analyses for the Clinician AMERICAN JOURNAL OF KIDNEY DISEASES Erickson, K. F., Winkelmayer, W. C. 2010; 56 (6): 1023-1025

    View details for DOI 10.1053/j.ajkd.2010.10.001

    View details for Web of Science ID 000284401800004

    View details for PubMedID 21094913

  • Off-Label Use of Phosphate Binders in Non-Dialysis-Dependent CKD AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Chertow, G. M. 2010; 56 (5): 813-816

    View details for DOI 10.1053/j.ajkd.2010.09.004

    View details for Web of Science ID 000283261700006

    View details for PubMedID 20970022

  • Temporal Trends in Adherence to Cardiovascular Medications in Elderly Patients After Hospitalization for Heart Failure CLINICAL PHARMACOLOGY & THERAPEUTICS Setoguchi, S., Choudhry, N. K., Levin, R., Shrank, W. H., Winkelmayer, W. C. 2010; 88 (4): 548-554

    Abstract

    Although the complexity of treatment regimens for patients with heart failure (HF) has increased over time because of the increased availability of efficacious medications, little is known about temporal trends in adherence to treatment regimens in these patients. We assessed trends in adherence to angiotensin-system blockers (ABs), ?-blockers (BBs), and spironolactone (SL) for HF in Medicare beneficiaries enrolled in two statewide pharmacy benefit programs from 1995 to 2004. The proportion of days covered (PDC) (%) was assessed after the first dispensing among users of an AB, BB, or SL. Proportions of full adherence (PDC >80%) did not change over time for ABs (54% in both 1996 and 2003) but increased slightly for BBs (from 47% in 1996 to 57% in 2003) and SL (from 31% in 1996 to 42% in 2003). Black race and dialysis treatment predicted poor adherence to any medications. Adherence to BBs and SL increased modestly over time, but overall nonadherence remained high.

    View details for DOI 10.1038/clpt.2010.139

    View details for Web of Science ID 000282064000028

    View details for PubMedID 20827266

  • Confusion about the Appropriate Use of Erythropoiesis-Stimulating Agents in Patients Undergoing Maintenance Dialysis SEMINARS IN DIALYSIS Winkelmayer, W. C. 2010; 23 (5): 486-491

    Abstract

    The introduction of recombinant erythropoietin for clinical use in dialysis patients in 1989 was considered a major milestone for the long-term treatment of these vulnerable patients. It was assumed that increasing hemoglobin concentrations would not only improve patient-reported outcomes, as shown in early trials, but also reduce morbidity and mortality. Evidence that has accumulated over the ensuing two decades has repeatedly contradicted this assumption. The presence of powerful stake holders, strong competing incentives, strong prior beliefs, and scarce and confusing evidence have maintained uncertainty about the appropriate treatment of patients with chronic kidney disease who are anemic, including those requiring dialysis. This commentary recalls the decades-long scientific and regulatory journey and attempts to make the case for the urgent need for potentially paradigm-shifting evidence generation to identify the therapeutic sweet spot that would maximize net benefits of treatment with erythropoiesis-stimulating agents in patients undergoing dialysis.

    View details for DOI 10.1111/j.1525-139X.2010.00768.x

    View details for Web of Science ID 000283718300011

    View details for PubMedID 21069924

  • Kidney Disease and Antihypertensive Medication Adherence: The Need for Improved Measurement Tools AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Winkelmayer, W. C. 2010; 56 (3): 423-426

    View details for DOI 10.1053/j.ajkd.2010.05.006

    View details for Web of Science ID 000281203200002

    View details for PubMedID 20728787

  • On the relative safety of intravenous iron formulations: New answers, new questions AMERICAN JOURNAL OF HEMATOLOGY Chertow, G. M., Winkelmayer, W. C. 2010; 85 (9): 643-644

    View details for DOI 10.1002/ajh.21835

    View details for Web of Science ID 000281601900002

    View details for PubMedID 20687100

  • Late referral to paediatric renal failure service impairs access to pre-emptive kidney transplantation in children ARCHIVES OF DISEASE IN CHILDHOOD Boehm, M., Winkelmayer, W. C., Arbeiter, K., Mueller, T., Aufricht, C. 2010; 95 (8): 634-638

    Abstract

    Timing of referral to subspecialists may be a major determinant for access to adequate treatment. Kidney transplantation is the preferred modality of renal replacement therapy (RRT) in children. In adults, delayed referral from general physicians to nephrologists reduced access to kidney transplantation. This study investigated the association between timing of referral and the likelihood of pre-emptive kidney transplantation in children.In this retrospective study, all patients in a tertiary paediatric nephrology centre were grouped according to first paediatric nephrologist visit (< or = 3 months prior to RRT was defined as 'late referral (LR)') and modality of first RRT. Descriptive, correlation and contingency statistics, Pearson's chi(2) test and logistic regression techniques were used for analysis.The median duration of nephrologists pre-RRT care of 111 children (50 girls and 61 boys; aged 8.0 years at first referral) was 1.5 (range 0-17.5) years. Thirty-two of 84 children who had their first visit >3 months prior to RRT were pre-emptively transplanted (38%), but only three of the 27 children with LR (11%; OR 4.9; 95% CI 1.37 to 17.7). Using a threshold of 12 months, the likelihood of pre-emptive kidney transplantation was still significantly influenced by timing of referral (OR 2.5; 95% CI 1.06 to 5.91).LR of children with chronic kidney disease to paediatric nephrology centre impairs the likelihood of receiving a pre-emptive kidney transplant. Specialised care of at least 12 months before the need for RRT arises is needed to allow for identification of and completion of the medical investigation of the living donor. Further studies using larger multicentre registries are needed to validate these single centre data.

    View details for DOI 10.1136/adc.2009.174581

    View details for Web of Science ID 000280197000016

    View details for PubMedID 20522470

  • Anemia Management and Mortality Risk in Incident Hemodialysis Patients Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Brookhart, M. A., Avorn, J., Winkelmayer, W. 2010; 304 (1): 42-43
  • Medication Issues in Older Individuals With CKD ADVANCES IN CHRONIC KIDNEY DISEASE Rifkin, D. E., Winkelmayer, W. C. 2010; 17 (4): 320-328

    Abstract

    Older US adults bear a substantial burden of chronic disease and take an average of five prescription and non-prescription medications per day. Recent data suggest that over 20% of older adults have chronic kidney disease (CKD) as defined by an impaired glomerular filtration rate. These individuals often have multiple comorbidities, including diabetes, hypertension, and cardiovascular disease. Although patients with CKD may receive substantial benefits from prescribed medications, they are also at high risk for adverse drug events and polypharmacy. In this review, we outline the risks and benefits of medication use in the CKD population as a specific case within geriatric pharmacoepidemiology as a framework.

    View details for DOI 10.1053/j.ackd.2010.03.005

    View details for Web of Science ID 000279804000006

    View details for PubMedID 20610359

  • HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival BMC NEPHROLOGY Younas, N., Wu, C. M., Shapiro, R., McCauley, J., Johnston, J., Tan, H., Basu, A., Schaefer, H., Smetanka, C., Winkelmayer, W. C., Unruh, M. 2010; 11

    Abstract

    The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival.We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival.36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models.In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.

    View details for DOI 10.1186/1471-2369-11-5

    View details for Web of Science ID 000283341100001

    View details for PubMedID 20359353

  • Impact of reimbursement changes on statin use among patients with diabetes in Austria WIENER KLINISCHE WOCHENSCHRIFT Winkelmayer, W. C., Asslaber, M., Bucsics, A., Burkhardt, T., Schautzer, A., Wieninger, P., Pogantsch, M., Brookhart, M. A. 2010; 122 (3-4): 89-94

    Abstract

    Statins have evolved as cornerstones of cardiovascular prevention in patients with diabetes. They are effective and can be cost-effective therapies, but increased use imposes a sizeable short-term burden on payors of health care. These have used various instruments to steer appropriate use of such treatment. It was the purpose of this study to examine the effect of two reimbursement policy changes of statin therapy in patients with diabetes in Austria.Retrospective cohort study; time-series analysis. From Austrian sickness funds claims, we identified a closed cohort of 68,953 patients receiving treatment for diabetes in the first quarter of 2004. From April 2004 - December 2005, we ascertained use of statins for each monthly interval. Patients were censored at death. We used pseudo-experimental time-series regression to evaluate the effect of two policy changes on statin use and cost overall, as well as on the use of preferred versus non-preferred statins.Statin use among Austrian patients with diabetes increased from 20.6% to 24.9% during the time period. A policy change essentially expanding reimbursement for statins from secondary to primary prevention among patients with diabetes had no discernible effect on the observed trends in statin use. Another policy change that imposed random chart review for appropriateness of prescription of non-preferred statins including atorvastatin 10 mg yielded a marked drop in use of atorvastatin 10 mg and increase in the use of preferred statins, while leaving overall trends in statin use unaffected.Quantitative evaluation of new policies can provide important insights into the effectiveness und utility of such changes.

    View details for DOI 10.1007/s00508-009-1292-6

    View details for Web of Science ID 000276456700007

    View details for PubMedID 20213375

  • ACE Inhibitor and Angiotensin II Type 1 Receptor Antagonist Therapies in Elderly Patients with Diabetes Mellitus Are They Underutilized? DRUGS & AGING Pappoe, L. S., Winkelmayer, W. C. 2010; 27 (2): 87-94

    Abstract

    Diabetes mellitus is highly prevalent in older adults in the industrialized world. These patients are at high risk of complications from diabetes, including diabetic kidney disease. ACE inhibitors and their newer cousins, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), are powerful medications for the prevention of progression of diabetic renal disease. Unfortunately, among the elderly, these medications have been underutilized. The reasons for this include physician concerns regarding patient age and limited life expectancy and potential complications of ACE inhibitor or ARB use, specifically an increase in creatinine levels and hyperkalaemia. As discussed in this article, there have been several studies that show that the effects of inhibition of the renin-angiotensin system can be beneficial for the treatment of cardiovascular disease and renal disease among elderly patients with diabetes and that the potential risks mentioned above are no greater in this group than in the general population. For these reasons, several professional societies recommend that elderly patients with diabetes and hypertension (systolic blood pressure >or=140 mmHg or diastolic blood pressure >or=90 mmHg) be treated with an ACE inhibitor or ARB (as is recommended for younger diabetics). Use of ACE inhibitors or ARBs is also recommended for those with cardiovascular disease or those who are at risk of cardiovascular disease. Furthermore, in the management of diabetic kidney disease in elderly patients, treatment with ACE inhibitors or ARBs is also recommended to reduce the risk or slow the progression of nephropathy. Renal function and potassium levels should be monitored within the first 12 weeks of initiation of these medications, with each dose increase, and on a yearly basis thereafter. This article summarizes the current guidelines on the use of ACE inhibitors and ARBs in older adults with diabetes, reviews the evidence for their use in the elderly population, and suggests potential reasons for the observed underuse of these powerful drugs in this vulnerable population.

    View details for Web of Science ID 000274870400001

    View details for PubMedID 20104936

  • Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis. Emerging themes in epidemiology Liem, Y. S., Wong, J. B., Hunink, M. M., de Charro, F. T., Winkelmayer, W. C. 2010; 7 (1): 1-?

    Abstract

    To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients.Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models.The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables.Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification.

    View details for DOI 10.1186/1742-7622-7-1

    View details for PubMedID 20459823

  • Effect of Hemodialysis Before Transplant Surgery on Renal Allograft Function-A Pair of Randomized Controlled Trials TRANSPLANTATION Kikic, Z., Lorenz, M., Sunder-Plassmann, G., Schillinger, M., Regele, H., Gyoeri, G., Muehlbacher, F., Winkelmayer, W. C., Boehmig, G. A. 2009; 88 (12): 1377-1385

    Abstract

    Hemodialysis immediately before kidney transplant surgery has been suggested to adversely affect early graft function. On the other hand, considering its profound antiinflammatory effects, a beneficial impact of regional citrate anticoagulation on the evolution of graft function can be speculated. We sought to assess the clinical impact of preoperative hemodialysis and dialysis anticoagulation in two related randomized trials.Eligible kidney transplant candidates with a serum potassium less than or equal to 5.0 mEq/L were randomized to receive dialysis or no dialysis before deceased donor transplantation. Patients with a potassium more than 5.0 mEq/L were randomized to receive dialysis with heparin or citrate anticoagulation. The primary endpoint was the estimated glomerular filtration rate (eGFR) at posttransplant day 5.The first comparison (56 vs. 54 patients) revealed no effect of dialysis on eGFR at day 5 (primary endpoint, 12 [interquartile range 5-36] vs. 13 [5-37] mL/min/1.73 m2, P=0.98), rates of delayed graft function (22% vs. 27%, P=0.66), cellular rejection (20% vs. 24%, P=0.65), and C4d-positive dysfunction (2% vs. 9%, P=0.11) or 1-year death-censored graft survival (89% vs. 91%, P=0.51). Comparing citrate with heparin anticoagulation (44 vs. 66 patients), no differences in eGFR at day 5 (17 [8-31] vs. 14 [6-38] ml/min/1.73 m2, P=0.57), delayed graft function (21% vs. 30%, P=0.28), cellular rejection (23% vs. 33%, P=0.29), and graft survival (90% vs. 88%, P=0.44) were found. For citrate anticoagulation, less C4d-positive rejection episodes (P=0.08) and higher 1-year eGFR levels (P=0.03) were observed.Pretransplant hemodialysis and anticoagulation may not affect early graft function in a meaningful way.

    View details for DOI 10.1097/TP.0b013e3181bc03ab

    View details for Web of Science ID 000273200000008

    View details for PubMedID 20029334

  • Greater Epoetin alfa (EPO) doses and short-term mortality risk among hemodialysis patients with hemoglobin levels less than 11 g/dL PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Bradbury, B. D., Do, T. P., Winkelmayer, W. C., Critchlow, C. W., Brookhart, M. A. 2009; 18 (10): 932-940

    Abstract

    We examined the association between high doses of Epoetin alfa (EPO), which are used to raise and maintain hemoglobin (Hb) levels within target ranges for hemodialysis patients, and short-term mortality risk using multivariable regression and an instrumental variable (IV) analysis.We identified 32 734 patients receiving hemodialysis in 786 facilities from a large US dialysis provider between July 2000 and March 2002 who received care for >4 consecutive months, and had an Hb < 11 g/dL in the third month. We assessed dose titrations following the Hb < 11 g/dL and characterized facilities based on the percentage of patients with dose titrations >25% (instrument). We assessed deaths during the subsequent 90 days and evaluated the EPO dose-mortality association using conventional linear and IV regression.The study population had a mean (SD) age of 60.4 (15.0) years; 48% were white, 42% were black and 51% were male. In unadjusted analyses, high EPO doses were associated with 90-day mortality risk (Risk Difference, RD = 3.0 per 100 persons, 95%CI:2.3-3.6); mortality risk was attenuated after adjustment for confounding (RD = 1.5 per 100 persons, 95%CI:0.8-2.2) and not associated with high EPO dose in the pooled IV analysis, though confidence intervals (CI) were wide (RD = -0.4 per 100 persons, 95%CI:-3.2-2.4).The difference in risk estimates between the adjusted linear regression and the IV regression suggests that the short-term mortality related to EPO dosing may be largely attributable to confounding-by-indication for higher doses. The IV method, which was employed to address the possibility of residual confounding, yielded near null though imprecise effect estimates.

    View details for DOI 10.1002/pds.1799

    View details for Web of Science ID 000271076200008

    View details for PubMedID 19572312

  • Chronic on Acute Renal Failure Long-term Implications of Severe Acute Kidney Injury JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Waikar, S. S., Winkelmayer, W. C. 2009; 302 (11): 1227-1229

    View details for Web of Science ID 000269797600036

    View details for PubMedID 19755705

  • Evolving Statistical Methods to Facilitate Evaluation of the Causal Association Between Erythropoiesis-Stimulating Agent Dose and Mortality in Nonexperimental Research: Strengths and Limitations AMERICAN JOURNAL OF KIDNEY DISEASES Bradbury, B. D., Brookhart, M. A., Winkelmayer, W. C., Critchlow, C. W., Kilpatrick, R. D., Joffe, M. M., Feldman, H. I., Acquavella, J. F., Wang, O., Rothman, K. J. 2009; 54 (3): 554-560

    Abstract

    Findings from randomized controlled trials examining the efficacy of therapy with erythropoiesis-stimulating agents (ESAs) to normalize hemoglobin levels in patients with chronic kidney disease or kidney failure have raised questions regarding the safety of this class of drugs. However, no trial to date has specifically assessed the safety of ESA-dosing algorithms used to achieve the lower hemoglobin targets typically using in clinical practice. Although a wealth of nonexperimental data is available for dialysis patients, analyses based on these data are more susceptible to confounding bias than randomized controlled trials. Conducting valid pharmacoepidemiologic studies of drug effects in hemodialysis patients is complicated by the extent of their comorbidities, frequent hospitalizations, various concomitant medications, and an exceedingly high mortality rate. The need for greater ESA doses for the treatment of anemia in sicker patients potentially and plausibly generates confounding by indication, the control of which is complicated by the presence of time-dependent confounding. Here, we describe sources of bias in nonexperimental studies of ESA therapy in hemodialysis patients and critically appraise analytical methods that may help minimize bias in such studies.

    View details for DOI 10.1053/j.ajkd.2009.05.010

    View details for Web of Science ID 000269640600023

    View details for PubMedID 19592144

  • Association Between Altitude and Mortality in Incident Dialysis Patients Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Winkelmayer, W. C., Brookhart, M. A. 2009; 301 (23): 2443-2443
  • Lessons from Geographic Variations in Predialysis Nephrology Care JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C. 2009; 20 (5): 930-932

    View details for DOI 10.1681/ASN.2009030318

    View details for Web of Science ID 000265959800005

    View details for PubMedID 19389840

  • Nonselective and Cyclooxygenase-2-Selective NSAIDs and Acute Kidney Injury AMERICAN JOURNAL OF MEDICINE Winkelmayer, W. C., Waikar, S. S., Mogun, H., Solomon, D. H. 2008; 121 (12): 1092-1098

    Abstract

    The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute kidney injury is well established, but it is less clear whether this risk is focused with specific agents. We undertook a large pharmacoepidemiologic analysis of the risk of acute kidney injury among older adults using nonselective NSAIDs or cyclooxygenase (COX)-2 inhibitors.Medicare beneficiaries from 2 large states with drug benefit were eligible for study. Patients were included if they filled a prescription for a nonselective NSAID or COX-2 inhibitor after more than 6 months without any such prescriptions and without a previous diagnosis of acute kidney injury. Incident acute kidney injury was ascertained from hospitalization claims within 45 days of initiating nonselective NSAID or COX-2 inhibitor therapy. Adjusted proportional hazards models estimated the relative risk of acute kidney injury associated with each agent compared with celecoxib.We included 183,446 patients whose mean age was 78 years; 80% were women. Acute kidney injury was identified in 870 (0.47%) of nonselective NSAID or COX-2 inhibitor users. The agents with significantly elevated risk compared with celecoxib were indomethacin (rate ratio [RR] = 2.23; 95% confidence interval [CI], 1.70-2.93), ibuprofen (RR = 1.73; 95% CI, 1.36-2.19), and rofecoxib (RR = 1.52; 95% CI, 1.26-1.83). These findings were robust in several subgroups.Acute kidney injury requiring hospitalization is a relatively rare adverse event among older adults after initiation of nonselective NSAIDs or COX-2 inhibitor treatment, observed in approximately 1 in 200 new users within 45 days. There seems to be a marked gradient of risk for acute kidney injury across agents, specifically for indomethacin, ibuprofen, and rofecoxib.

    View details for DOI 10.1016/j.amjmed.2008.06.035

    View details for Web of Science ID 000261985100030

    View details for PubMedID 19028206

  • Trends in adherence to secondary prevention medications in elderly post-myocardial infarction patients PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Choudhry, N. K., Setoguchi, S., Levin, R., Winkelmayer, W. C., Shrank, W. H. 2008; 17 (12): 1189-1196

    Abstract

    Poor levels of medication adherence for patients with coronary heart disease (CHD) have been documented but it is unclear whether adherence has improved over time.We assembled a retrospective cohort of lower-income Medicare beneficiaries who were discharged from the hospital after their first acute myocardial infarction (MI) between 1 January 1995 and 31 December 2003. For patients prescribed a statin, ACEI/ARB, beta-blocker, and all 3 of these medications after the hospital discharge, we evaluated medication adherence by determining the proportion of days covered (PDC) for each medication in the subsequent year.Our cohort consisted of a total of 33 646 patients. Adherence rates for statins and beta-blockers, but not ACEI/ARB, increased significantly over time but remained suboptimal. For example, among those patients that received a statin after discharge, 38.6% were fully adherent with therapy in 1995 in contrast to 56.2% in 2003 (p value for trend<0.001). Of patients prescribed all 3 of statin, beta-blocker, and ACEI/ARB, 29.1% and 46.4% were fully adherent in 1995 and 2003, respectively (p value for trend<0.001).Our analysis demonstrates statistically significant but modest improvements in medication adherence for statins and beta-blockers, but not ACEI/ARBs, among patients discharged from hospital after acute MI. Despite these improvements, rates of non-adherence to these highly effective therapies remain extremely high. Given the health and economic consequences of non-adherence, the development of cost-effective strategies to improve medication adherence should be a clear priority.

    View details for DOI 10.1002/pds.1671

    View details for Web of Science ID 000261912200008

    View details for PubMedID 18956426

  • Comparison of Cardiovascular Outcomes in Elderly Patients With Diabetes Who Initiated Rosiglitazone vs Pioglitazone Therapy ARCHIVES OF INTERNAL MEDICINE Winkelmayer, W. C., Setoguchi, S., Levin, R., Solomon, D. H. 2008; 168 (21): 2368-2375

    Abstract

    Recent meta-analyses have raised the possibility that rosiglitazone maleate may increase the risk of ischemic cardiovascular events, whereas pioglitazone hydrochloride could not be linked to such a risk. We compared cardiovascular outcomes and mortality between patients initiating pioglitazone vs rosiglitazone therapy.We assembled an inception cohort of Medicare beneficiaries older than 65 years with state-sponsored prescription drug benefits who had diabetes mellitus and initiated treatment with rosiglitazone or pioglitazone between January 1, 2000, and December 31, 2005. The study outcomes included all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure.Of 28 361 patients selected, 50.3% initiated treatment with pioglitazone and 49.7% with rosiglitazone. Most baseline characteristics were similar between the groups. As preferred in drug safety research, we censored patients at crossover or at 60 days after discontinuation of therapy with their study drug; during 29 060 person-years of follow-up, 1869 patients died. After adjustment for a large number of patient characteristics, Cox regression models revealed 15% greater mortality among patients who initiated therapy with rosiglitazone compared with pioglitazone (95% confidence interval, 5%-26%). Use of rosiglitazone was also associated with a 13% greater risk of congestive heart failure (95% confidence interval, 1%-26%). No differences between the 2 drugs were found in their rates of myocardial infarction or stroke.Our findings from a large population-based cohort of US seniors are compatible with an increased risk of all-cause mortality and congestive heart failure in patients initiating therapy with rosiglitazone compared with similar patients initiating therapy with pioglitazone. Limitations of this study include residual confounding due to its nonrandomized nature.

    View details for Web of Science ID 000261151700013

    View details for PubMedID 19029503

  • Associations of kidney function with cardiovascular medication use after myocardial infarction CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Levin, R., Setoguchi, S. 2008; 3 (5): 1415-1422

    Abstract

    It is unknown whether adherence to recommended medications after myocardial infarction (MI) differs by kidney function.This was a retrospective cohort study of older patients who were discharged after MI in two Eastern states between 1995 and 2004. Patients were categorized as having ESRD, having chronic kidney disease (CKD), and being free from diagnosed CKD. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), beta blockers (BB), and statins was assessed within 30 d after discharge. Good adherence was defined as proportion of days covered >80% during the first year after discharge.Compared with patients with no CKD, patients with CKD had 22% lower adjusted use of ACEI/ARB but similar rates of BB and statin use. Patients with ESRD experienced 43% lower ACEI/ARB and 17% lower statin use. Only 64% (BB), 57% (statins), and 54% (ACEI/ARB) of patients had good 1-yr adherence. Adherence was similar between patients with CKD and with no CKD for all study drugs. Fewer patients with ESRD had good adherence to BB.With the exception of lower ACEI/ARB use in patients with CKD, we found no differences between patients with CKD and with no CKD in their use of and adherence to these cardiovascular medications after MI. Patients with ESRD experienced lower use of ACEI/ARB and statins and lower adherence to BB regimens. Postulated differences in medication use after MI across levels of kidney function are unlikely to explain the observed differences in long-term outcomes.

    View details for DOI 10.2215/CJN.02010408

    View details for Web of Science ID 000258757500031

    View details for PubMedID 18614775

  • The effect of altitude on dosing and response to erythropoietin in ESRD JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Brookhart, M. A., Schneeweiss, S., Avorn, J., Bradbury, B. D., Rothman, K. J., Fischer, M., Mehta, J., Winkelmayer, W. C. 2008; 19 (7): 1389-1395

    Abstract

    For poorly understood reasons, patients with end-stage renal disease (ESRD) differ substantially in their response to treatment with recombinant erythropoietin (EPO). Because hypoxia influences many of the biologic pathways involved in erythropoiesis, the altitude at which a patient lives may affect the dose-response relationship of EPO. In this retrospective cohort study, clinical data from 341,737 incident hemodialysis patients registered in the U.S. Renal Data System were combined with elevation data from the U.S. Geological Survey to address this question. Higher altitude was associated with smaller EPO doses and higher hematocrit levels. For example, compared with patients at sea level, patients living above 6000 ft received 19% less EPO (12.9 versus 15.9 thousand units/wk) but had hematocrit levels 1.1 points higher (35.7% versus 34.6%). These associations were found within subgroups defined by sex, race, age, calendar time, cause of ESRD, and dialysis center profit status, and persisted after adjustment for various potential confounding factors. Furthermore, resistance to EPO decreased with elevation. Our results suggest that ESRD patients living at high altitude either increase endogenous EPO production or respond better to endogenous and exogenous EPO.

    View details for DOI 10.1681/ASN.2007111181

    View details for Web of Science ID 000257262600021

    View details for PubMedID 18385423

  • Gender differences in the management and prognosis of myocardial infarction among patients >= 65 years of age AMERICAN JOURNAL OF CARDIOLOGY Setoguchi, S., Solomon, D. H., Levin, R., Winkelmayer, W. C. 2008; 101 (11): 1531-1536

    Abstract

    Conflicting evidence exists regarding gender differences in the management and outcomes of myocardial infarctions (MIs). In this study, it was hypothesized that the management and outcomes of MIs would not differ by gender after proper adjustment for age, access to care, MI characteristics, and co-morbidities. Data from a published MI validation study, which sampled 2,200 MI hospitalizations in Medicare beneficiaries with the prescription drug benefit for detailed hospital chart review, were used. Gender differences in the use of MI-related procedures and recommended cardiovascular medications as well as short- and long-term mortality were assessed using multivariate regression. A total of 1,625 patients were identified (80% women) with confirmed MIs for whom complete clinical information was available. Compared with men, women were older and had higher body mass index. Women were more likely to have diabetes, renal dysfunction, and depression, but less likely to have had previous MIs, chronic lung disease, cancer, and to use tobacco. The characteristics of the index MIs were similar, except for non-Q-wave MIs being more common in men. The management of the MIs during admission was similar. During follow-up of up to 6.6 years, men were 40% more likely to die than women (95% confidence interval 21% to 62%), but no mortality difference was observed in patients aged 65 to 74 years (hazard ratio 0.92, 95% confidence interval 0.62 to 1.36), whereas in those aged > or =75 years, men were more likely to die than women (hazard ratio 1.54, 95% confidence interval 1.30 to 1.82). In conclusion, for older patients, the management of MIs did not significantly differ between men and women. Men, especially those aged > or =75 years, however, had worse short- and long-term prognoses compared with women of a similar age. The mortality was highest and the gender effect was more pronounced during the MI hospitalizations.

    View details for DOI 10.1016/j.amjcard.2008.02.033

    View details for Web of Science ID 000256450700002

    View details for PubMedID 18489928

  • Educational level as a determinant of access to and outcomes after kidney transplantation in the United States AMERICAN JOURNAL OF KIDNEY DISEASES Schaeffner, E. S., Mehta, J., Winkelmayer, W. C. 2008; 51 (5): 811-818

    Abstract

    Disparities in access to kidney transplantation exist, yet few studies investigated educational level as a determinant of access to and outcomes after kidney transplantation.Prospective cohort study.Nationally representative sample of incident US dialysis patients, in which 3,245 patients reported their educational level.Educational level, categorized as some high school, high school graduate, some college, and college graduate.Access to kidney transplantation was defined as time from first dialysis treatment to: (1) the day of being wait-listed and (2) first kidney transplantation. Outcomes after kidney transplantation were: (3) all-cause mortality and graft failure ([4] all-cause and [5] death censored). Using Cox regression, we studied the relationship between predialysis educational level and access to and outcomes after kidney transplantation.During follow-up, 692 patients were wait-listed and 670 underwent kidney transplantation. Of those, 164 died and 241 lost their allograft (121 from nondeath causes). After multivariate adjustment, college graduates experienced 3 times greater rates of wait-listing (hazard ratio, 2.81; 95% confidence interval, 2.21 to 3.58) or kidney transplantation (hazard ratio, 3.06; 95% confidence interval, 2.38 to 3.92) compared with patients without a high school degree (P for trend across educational level for both outcomes < 0.001). Although mortality was not associated with educational level, increased rates of death-censored allograft loss were observed with less education (P for trend = 0.03).Not a randomized study.The latter finding is novel and important and requires confirmation. Its possible mechanisms (eg, adherence to immunosuppressants) warrant additional study.

    View details for DOI 10.1053/j.ajkd.2008.01.019

    View details for Web of Science ID 000255490200015

    View details for PubMedID 18436092

  • Long-term trends of angiotensin-converting enzyme inhibitor and angiotensin-receptor blocker use after heart failure hospitalization in community-dwelling seniors INTERNATIONAL JOURNAL OF CARDIOLOGY Setoguchi, S., Levin, R., Winkelmayer, W. C. 2008; 125 (2): 172-177

    Abstract

    Despite multiple trials demonstrating the benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) for heart failure (HF) patients with systolic dysfunction, studies have reported underuse of these drugs. Little is known about recent trends in the use of ACEI/ARB in community-dwelling seniors.Using administrative data from pharmacy assistance programs and Medicare in two states, we identified all patients hospitalized for HF between 1995 and 2004 who survived >or=90 days after discharge. The study outcomes were filled prescriptions for an ACEI or ARB within 90 days after discharge. We assessed age, gender, race, and comorbidities. Multivariate modified Poisson regression was used to analyze temporal trends.Of 54,453 patients identified, 26,166 (48%) filled prescriptions for ACEIs/ARBs within 90 days after discharge from HF, but utilization of these drugs did not increase during the decade studied. Among those who were on ACEI/ARB before the index hospitalization, 74% filled at least one ACEI/ARB prescription within 90 days after the hospitalization. These results were similar among the subgroup of HF patients with prior MI.Use of ACEI/ARB after discharge from HF hospitalization in seniors did not increase over the decade of observation and may still be inadequate.

    View details for DOI 10.1016/j.ijcard.2007.10.009

    View details for Web of Science ID 000255990200006

    View details for PubMedID 17997175

  • Approaching the end of the homocysteine hype? AMERICAN JOURNAL OF KIDNEY DISEASES Sunder-Plassmann, G., Winkelmayer, W. C., Foedinger, M. 2008; 51 (4): 549-553

    View details for DOI 10.1053/j.ajkd.2008.01.007

    View details for Web of Science ID 000254874400005

    View details for PubMedID 18371530

  • Improvements in long-term mortality after myocardial infarction and increased use of cardiovascular drugs after discharge JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Setoguchi, S., Glynn, R. J., Avorn, J., Mittleman, M. A., Levin, R., Winkelmayer, W. C. 2008; 51 (13): 1247-1254

    Abstract

    We sought to assess the relationship between increasing use of cardiovascular medications and trends in long-term prognosis after myocardial infarction (MI) in the elderly.During the past decade, statins, beta-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs) have been increasingly used after MI. However, little is known about the relationship between increasing use of these medications and improvements in prognosis after MI.Using data from pharmacy assistance programs and Medicare in 2 states (1995 to 2004), we identified patients with MI who survived >or=30 days after discharge. We assessed age, gender, race, comorbidities, and coronary interventions during the MI hospitalization and recorded filled prescriptions for statins, BBs, ACEIs/ARBs, or antiplatelet agents within 30 days after discharge. All patients were tracked until they died or until the end of the eligibility/study period. We built multivariate Cox proportional hazards regression models to assess trends in long-term mortality and the contribution to increasing medication use after MI.Of 21,484 patients identified, 12,142 died during 74,982 person-years of follow-up. After adjusting for demographics and comorbidities, we found that mortality after MI decreased significantly from 1995 to 2004 (hazard ratio for annual trend 0.97; 95% confidence interval 0.97 to 0.98), a 3% reduction in mortality each year. Adjusting for the use of statins, BBs, ACEIs/ARBs, and antiplatelet drugs after discharge completely eliminated the association between time trend and mortality (hazard ratio 1.00; 95% confidence interval 0.99 to 1.01).The observed improvement in long-term mortality in elderly patients with MI may be mainly due to increased use of cardiovascular medications after discharge.

    View details for DOI 10.1016/j.jacc.2007.10.063

    View details for Web of Science ID 000254637000002

    View details for PubMedID 18371553

  • Phosphate binder choice in dialysis patients: A call for evidence-based rather than marketing-based clinical practice AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Tonelli, M. 2008; 51 (3): 362-365

    View details for DOI 10.1053/j.ajkd.2008.01.004

    View details for Web of Science ID 000254799900005

    View details for PubMedID 18295050

  • Posttransplantation anemia: Management and rationale CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Chandraker, A. 2008; 3: S49-S55

    Abstract

    In recent years, there has been an increasing interest in studying the anemia that occurs after kidney transplantation. Although many of the guidelines for the treatment of kidney transplant patients, including those for anemia, are extrapolated from recommendations for patients with chronic kidney disease, there are important differences in the cause of and response to anemia in kidney transplant recipients. In addition to the correlation of anemia with kidney function as in native renal disease, many other factors are associated with the development of anemia after transplantation, including the use of medications and the inflammation/immune response. Given the lack of large, well-designed, prospective studies, the consequences of anemia, the response to treatment, and the cost-effectiveness of treatment in the posttransplantation setting are also poorly understood.

    View details for DOI 10.2215/CJN.03290807

    View details for Web of Science ID 000253822600004

    View details for PubMedID 18309003

  • Use of recommended medications after myocardial infarction in Austria EUROPEAN JOURNAL OF EPIDEMIOLOGY Winkelmayer, W. C., Bucsics, A. E., Schautzer, A., Wieninger, P., Pogantsch, M. 2008; 23 (2): 153-162

    Abstract

    Guidelines recommend long-term use of beta-blockers (BB), statins, and angiotensin-converting-enzyme-inhibitors or angiotensin-receptor-blockers (ACEI/ARB) after myocardial infarction (MI), but data on their use after discharge are scarce. From Austrian sickness funds claims, we identified all acute MI patients who were discharged within 30 days and who survived >or=120 days after MI in 2004. We ascertained outpatient use of ACEI/ARBs, BBs, statins, and aspirin from all filled prescriptions between discharge and 120 days post MI. Comorbidities were ascertained from use of indicator drugs during the preceding year. Multivariate logistic regression was used to evaluate the independent determinants of study drug use. We evaluated 4,105 MI patients, whose mean age was 68.8 (+/-13.2) years; 59.5% were men. Within 120 days after MI, 67% filled prescriptions for ACE/ARBs, 74% for BBs, and 67% for statin. While 41% received all these classes and 34% two, 25% of patients received only one or none of these drugs. Older age and presence of severe mental illness were associated with lower use of all drug classes. Diabetics had greater ACEI/ARB use. Fewer BBs were used in patients with obstructive lung disease. Statin use was lower in patients using treatment for congestive heart failure (all P<0.001). We conclude that recommended medications were underused in Austrian MI survivors. Quality indicators should be established and interventions be implemented to ensure maximum secondary prevention after MI.

    View details for DOI 10.1007/s10654-007-9212-4

    View details for Web of Science ID 000252624800010

    View details for PubMedID 18064529

  • Medication adherence after myocardial infarction: A long way left to go JOURNAL OF GENERAL INTERNAL MEDICINE Choudhry, N. K., Winkelmayer, W. C. 2008; 23 (2): 216-218

    View details for DOI 10.1007/s11606-007-0478-8

    View details for Web of Science ID 000252944600019

    View details for PubMedID 18183470

  • Benzodiazepine use and mortality of incident dialysis patients in the United States KIDNEY INTERNATIONAL Winkelmayer, W. C., Mehta, J., Wang, P. S. 2007; 72 (11): 1388-1393

    Abstract

    Benzodiazepines and other omega-receptor agonists are frequently used for sleep and anxiety disorders. We studied the rates, correlates, and safety of individual benzodiazepines and zolpidem use from the records of 3690 patients in a national cohort of Dialysis Morbidity and Mortality Study Wave 2 data. We assessed drug utilization and an association between drug use and all-cause mortality. Overall, 14% of incident dialysis patients used a benzodiazepine or zolpidem. Women, Caucasians, current smokers, and patients with chronic obstructive pulmonary disease were more likely to use these drugs, whereas patients with cerebrovascular disease were less likely to use these drugs. In adjusted analyses, benzodiazepine or zolpidem use was associated with a 15% higher mortality rate. Chronic obstructive pulmonary disease significantly modified this association, suggesting that these patients were at higher risk. No association was found between benzodiazepine use and greater risk for hip fracture. We conclude that benzodiazepine or zolpidem use is common in incident dialysis patients and may be associated with greater mortality. Further studies are needed to elucidate the safety of these drugs in the dialysis population, which may lead to cautious and restrictive utilization of omega-receptor agonists in dialysis patients.

    View details for DOI 10.1038/sj.ki.5002548

    View details for Web of Science ID 000250955900019

    View details for PubMedID 17851463

  • Ten-year trends of cardiovascular drug use after myocardial infarction among community-dwelling persons >= 65 years of age AMERICAN JOURNAL OF CARDIOLOGY Setoguchi, S., Glynn, R. J., Avorn, J., Levin, R., Winkelmayer, W. C. 2007; 100 (7): 1061-1067

    Abstract

    Guidelines for post-myocardial infarction (MI) management emphasize treatment with statins, beta blockers (BBs), and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Little is known about the temporal trends and racial differences in such use after discharge. This study assessed temporal trends and racial differences in the use of statins, BBs, and ACEIs or ARBs after MI discharge in community-dwelling seniors. Administrative data from pharmacy assistance programs and Medicare in 2 states (1995 to 2004) were used to identify all patients hospitalized for MI who survived > or =90 days after discharge. Age, gender, race, co-morbidities, and MI-specific procedures during hospitalization were assessed. The study outcomes were filled prescriptions for any statin, BB, or ACEI or ARB <90 days after discharge. Multivariate regression was used for trend and racial difference analyses. Of 19,368 patients identified, 6,577 (34.0%) filled prescriptions for statins, 12,387 (64.0%) for BBs, and 9,934 (51.3%) for ACEIs or ARBs <90 days after MI discharge. The use of these drugs increased from 1995 to 2004, most steeply for statins (11% to 61%), less so for BBs (47% to 80%), and least for ACEIs or ARBs (46% to 58%) (all p for trend <0.001). Black patients were 14% and 5% less likely to receive statins and BBs, respectively (all p <0.05). No evidence of an interaction between race and time trend was found. In conclusion, the use of cardiovascular medications after discharge from MI hospitalization in older patients may still be inadequate but has increased over time. The underuse of statins and BBs was marked in black patients and did not improve over time.

    View details for DOI 10.1016/j.amjcard.2007.04.052

    View details for Web of Science ID 000249897700004

    View details for PubMedID 17884362

  • Cardiovascular risk and the thiazolidinediones - Deja vu all over again? JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Solomon, D. H., Winkelmayer, W. C. 2007; 298 (10): 1216-1218

    View details for Web of Science ID 000249374200030

    View details for PubMedID 17848659

  • Early erythropoietin therapy is associated with improved growth in children with chronic kidney disease PEDIATRIC NEPHROLOGY Boehm, M., Riesenhuber, A., Winkelmayer, W. C., Arbeiter, K., Mueller, T., Aufricht, C. 2007; 22 (8): 1189-1193

    Abstract

    Recent registry reports related short stature at the time of dialysis initiation to increased morbidity and mortality. Growth may therefore serve as an overall indicator of disease severity and therapy quality in pediatric chronic kidney disease. We studied whether early correction of uremic complications such as anemia was associated with growth failure. In this retrospective cohort study, we assessed demographic, diagnostic, and therapeutic variables at first referral and at dialysis initiation in all children with congenital renal diseases who initiated chronic dialysis at our clinic between 1994-2004. Outcomes were indicators of growth at referral and first dialysis as well as interval growth. Correlation and logistic regression techniques were used for analysis. We studied 47 children (24 boys, 23 girls) who were 7.1 years of age and had a mean glomerular filtration rate (GFR) of 25 ml/min per 1.73 m2 at first visit. Time to dialysis was a median 2.5 years. At first referral, 36% of children had severe growth failure with standard deviation score (SDS) height<-2. Stature at that time point was correlated with GFR (rho=0.37, p=0.03) and predicted stature at dialysis initiation (rho=0.81, p<0.001). Catch-up growth during predialysis care was achieved in 40% of the children and independently associated with both hemoglobin (OR=1.85, p=0.04) and erythropoietin therapy (OR=13.6, p<0.05) at first referral. This study confirms the disappointingly high prevalence of growth retardation in children with chronic kidney disease. Initial hemoglobin and early erythropoietin prescription were the only (modifiable) variables associated with improved growth. Almost two thirds of referred children, however, experienced no catch-up growth during follow-up. Further study is needed to better define the optimal timing and intensity of nephrologist care in children with kidney disease.

    View details for DOI 10.1007/s00467-007-0472-8

    View details for Web of Science ID 000247310400014

    View details for PubMedID 17394020

  • Statins in elderly patients with acute coronary syndrome: an analysis of dose and class effects in typical practice HEART Choudhry, N. K., Levin, R., Winkelmayer, W. C. 2007; 93 (8): 945-951

    Abstract

    To compare the effectiveness of statins of different treatment intensity used to treat elderly patients with acute coronary syndrome (ACS) in typical care settings.Retrospective cohort study using linked hospital and pharmacy claims data.Statewide pharmacy benefits programmes in Pennsylvania and New Jersey.18,311 Medicare patients discharged alive after ACS who received a prescription for a statin within 90 days of hospital discharge.Using multivariable and propensity-matched Cox proportional hazards regression models, patients who were prescribed high-intensity and moderate-intensity statins were compared based on the drug-dose combination that they initially received. Individual drug-dose combinations were also compared. Our primary outcome was the composite of all-cause death or recurrent ACS.Patients who received moderate-intensity statins were as likely to experience a primary outcome as patients treated with high-intensity statins (adjusted HR 1.02, 95% CI 0.96 to 1.08). Propensity matching did not change the results. Individually, all moderate-intensity statins were as effective as high-intensity atorvastatin with the exception of lovastatin (adjusted HR 1.22, 95% CI 1.09 to 1.36). Similarly, all high-intensity statins seem as effective as high-intensity atorvastatin but the CIs surrounding these estimates were wide.This analysis of elderly patients with ACS treated in typical care settings does not demonstrate the superiority of high-intensity over moderate-intensity statin treatment or significant differences among individual statins.

    View details for DOI 10.1136/hrt.2006.110197

    View details for Web of Science ID 000248054400018

    View details for PubMedID 17344334

  • Renal dysfunction increases the risk of saphenous vein graft occlusion: Results from the Post-CABG trial ATHEROSCLEROSIS Wellenius, G. A., Mukamal, K. J., Winkelmayer, W. C., Mittleman, M. A. 2007; 193 (2): 414-420

    Abstract

    Saphenous vein grafts are common among patients with a history of coronary artery bypass graft (CABG) surgery. Chronic kidney disease (CKD) is an established cardiovascular risk factor, but its role in graft disease has not been evaluated.The Post-CABG Trial randomized 1351 patients who had undergone CABG surgery 1-11 years earlier to high- or low-dose lovastatin and to low-dose warfarin or placebo. Coronary angiography was conducted at baseline and after a median follow-up time of 4.2 years. Subjects were grouped according to their baseline estimated glomerular filtration rate (eGFR). The primary trial endpoint was significant graft disease progression assessed angiographically. Additional pre-defined endpoints included occlusion of grafts patent at baseline, change in minimum lumen diameter, and a composite endpoint of recurrent clinical events. Decreasing eGFR was associated with an increased risk of graft occlusion (P(trend)=0.040), but not substantial atherosclerotic progression (P(trend)=0.30), per-graft change in minimum lumen diameter (P(trend)=0.067), or recurrent clinical events (P(trend)=0.86). We did not observe significant effect modification of treatment effects by the presence of CKD.CKD may be associated with increased risk of atherosclerotic plaque disruption rather than atherosclerotic progression in saphenous vein grafts.

    View details for DOI 10.1016/j.atherosclerosis.2006.07.008

    View details for Web of Science ID 000248961200024

    View details for PubMedID 16905139

  • A J-shaped association between high-sensitivity C-reactive protein and mortality in kidney transplant recipients TRANSPLANT INTERNATIONAL Winkelmayer, W. C., Schaeffner, E. S., Chandraker, A., Kramar, R., Rumpold, H., Sunder-Plassmann, G., Foedinger, M. 2007; 20 (6): 505-511

    Abstract

    In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated with increased mortality, but data on this association within the high-sensitivity (hs) range of CRP (<5 mg/l) are lacking. We prospectively studied 710 prevalent and stable KTR over >6 years. We thawed frozen plasma and measured baseline hs-CRP using an ultrasensitive assay. Detailed clinical and demographic baseline characteristics were available for study. We stratified patients by quartile of hs-CRP within the hs range (<5 mg/l), and also included KTRs whose hs-CRP was above the hs range (>5-10 and >10 mg/l). We used multivariate proportional hazards models to test for independent associations. After careful multivariate adjustment, we found a J-shaped association between hs-CRP and mortality. Compared with KTR whose hs-CRP was in the second lowest quartile of hs-CRP (0.06-1.26 mg/l), patients in the lowest quartile (<0.06 mg/l) had more than twice their mortality risk (HR = 2.07; 95% CI: 1.05-4.07), as did patients whose hs-CRP was > or =2.44 mg/l (all HRs >2.27). No association was found between hs-CRP and death-censored allograft loss. In contrast to the general population, the association between hs-CRP and mortality in KTRs is not linear, but J-shaped, suggesting that KTRs with very low hs-CRP may also be at increased risk of death.

    View details for DOI 10.1111/j.1432-2277.2007.00472.x

    View details for Web of Science ID 000246245100004

    View details for PubMedID 17362474

  • Clinical presentation of myocardial infarction contributes to lower use of coronary angiography in patients with chronic kidney disease KIDNEY INTERNATIONAL Charytan, D. M., Setoguchi, S., Solomon, D. H., Avorn, J., Winkelmayer, W. C. 2007; 71 (9): 938-945

    Abstract

    Patients with chronic kidney disease (CKD) have high mortality following myocardial infarction (MI), but are less likely to undergo coronary angiography than those without CKD. Whether this phenomenon is explained by differences in the presentation of MI or by bias against performing coronary angiography in patients with CKD is unclear. We examined the clinical presentation of 1876 elderly patients who presented with MI and categorized them by estimated glomerular filtration rate: >60 ml/min (no/mild CKD), 30-60 ml/min (CKD Stage 3) or <30 ml/min (CKD Stage 4/5). Compared with patients with no/mild CKD, patients with CKD Stage 3 or Stage 4/5 had more comorbidity, greater prior nursing home use, and higher frequency of conduction abnormalities or anterior infarction. By contrast, peak creatinine kinase-MB fraction (CK-MB) concentrations were lower and ST-elevation MI was less common in patients with CKD Stage 3 or Stage 4/5. In univariate analyses, patients with CKD Stage 4/5 (odds ratio (OR)=0.34, 95% confidence interval (CI): 0.23-0.50) or Stage 3 (OR=0.57, 95% CI: 0.45-0.73) were markedly less likely to undergo angiography than subjects with no/mild CKD. After multivariable adjustment, the association of CKD Stage 3 with the use of coronary angiography was attenuated (OR=0.78, 95% CI: 0.60-1.03), but CKD Stage 4/5 remained strongly associated with lower use (OR=0.52, 95% CI: 0.34-0.80). Clinical features of MI are different in patients with and without CKD and may partly explain the low use of angiography in patients with CKD Stage 3. However, the clinical features of MI do not account for its underuse in MI patients with CKD Stages 4/5. Whether reduced use of angiography in patients with advanced CKD is justified must be evaluated in formal risk-benefit analyses.

    View details for DOI 10.1038/sj.ki.5002159

    View details for Web of Science ID 000246300100016

    View details for PubMedID 17342183

  • Impact of Medicaid prior authorization on angiotensin-receptor blockers: can policy promote rational prescribing? Health affairs Fischer, M. A., Choudhry, N. K., Winkelmayer, W. C. 2007; 26 (3): 800-807

    Abstract

    Prescription drug cost containment is a key health policy priority. State Medicaid programs have implemented policies requiring prior authorization before paying for angiotensin-receptor blockers (ARBs), a costly class of blood pressure medications. We examined the impact of these policies on drug use. We found that policies using a stepped-therapy approach reduced ARB use by 1.6 percent when first implemented and decreased the subsequent trend in ARB use by 1.3 percent per quarter; alternative approaches were unsuccessful. These findings have important implications for the development of rational drug reimbursement policy under Medicare Part D and other health insurance plans.

    View details for PubMedID 17485759

  • Nononcologic use of human recombinant erythropoietin therapy in hospitalized patients ARCHIVES OF INTERNAL MEDICINE Fischer, M. A., Morris, C. A., Winkelmayer, W. C., Avorn, J. 2007; 167 (8): 840-846

    Abstract

    Human recombinant erythropoietin (rHuEPO) is widely used to stimulate red blood cell production in patients with anemia due to cancer, renal disease, and other medical conditions, but concern has grown about its overuse and potential for harm. Little is known about the nature of rHuEPO use in hospitalized patients who receive rHuEPO therapy for nononcologic indications.We reviewed the drug utilization data from a large academic medical center for all patients admitted during 3 years to identify all patients without cancer who received at least 1 dose of rHuEPO, including their age and sex; diagnoses; hematocrit and hemoglobin and iron levels; and use of supplemental iron. We also compared the rates of laboratory testing and iron supplementation in patients with and without chronic kidney disease (CKD).A total of 1360 distinct patients with 3094 hospitalizations received at least 1 dose of rHuEPO. In 2959 admissions for which hematocrit was determined within 14 days before rHuEPO use, mean values were less than 33% in 1792 (61%) and greater than 36% in 553 (19%). Patients with CKD were more likely than patients without CKD to receive rHuEPO with hematocrit greater than 36% (22% vs 8%; P<.001). Monitoring of iron status was more common in patients with CKD than in those without CKD (64% vs 45%; P <.001). Almost one fourth (23%) of rHuEPO recipients in whom iron levels were measured had absolute iron deficiency (serum ferritin concentration <100 ng/mL). In patients with CKD, only about half (54%) had adequate iron stores at the time of rHuEPO administration; this rate was even lower in patients without CKD (33%; P<.001). Only 66% of patients with documented iron deficiency who were receiving rHuEPO also received concomitant iron supplementation; this rate did not differ between patients with or without CKD.There is significant variability in the degree of anemia, completeness of iron measurement, and use of iron supplementation in hospitalized patients without cancer who are prescribed rHuEPO. Our results identify potential targets for quality improvement in patients both with and without CKD.

    View details for Web of Science ID 000245903100015

    View details for PubMedID 17452549

  • Predialysis nephrologist care and access to kidney transplantation in the united states AMERICAN JOURNAL OF TRANSPLANTATION Winkelmayer, W. C., Mehta, J., Chandraker, A., Owen, W. F., Avorn, J. 2007; 7 (4): 872-879

    Abstract

    Predialysis nephrologist care is associated with morbidity and mortality in incident dialysis patients, but the relationship with access to kidney transplantation (KT) is unclear. From a national study of incident US dialysis patients, we identified 2253 patients with detailed information about predialysis care, sociodemographic characteristics and comorbidities. We used multivariate Cox proportional hazards models to study associations between predialysis nephrology care and two outcomes: time from first dialysis to the first day on the KT wait-list, and time to first KT. Two-thirds of patients first encountered a nephrologist >3 months prior to dialysis and one-third

    View details for DOI 10.1111/j.1600-6143.2006.01689.x

    View details for Web of Science ID 000245151500019

    View details for PubMedID 17391130

  • Prognostic associations of serum calcium, phosphate and calcium phosphate concentration product with outcomes in kidney transplant recipients TRANSPLANT INTERNATIONAL Schaeffner, E. S., Foedinger, M., Kramar, R., Sunder-Plassmann, G., Winkelmayer, W. C. 2007; 20 (3): 247-255

    Abstract

    Disturbances in calcium and phosphate metabolism have been linked to increased mortality in hemodialysis patients, but not in kidney transplant recipients (KTR). We enrolled 733 KTR from the Vienna General Hospital into this study. Detailed demographic, clinical, laboratory, and transplant-related information was collected at baseline. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, we examined the independent associations between serum calcium, serum phosphate, and calcium phosphate (CaPO(4)) product with the outcomes of death from any cause and kidney allograft loss. Over a median follow-up of >6 years, 154 patients died and 259 kidney allografts were lost. Associations with serum calcium, phosphate concentrations, and CaPO(4) product concentrations were found for allograft loss, but not for patient mortality. Patients in the highest quintile of phosphate concentration and CaPO(4) product had an increased risk for allograft loss compared with patients in the lowest quintile of these parameters (hazards ratio, HR = 2.15; 95% confidence interval, CI: 1.36-3.40 and HR = 1.72; 95% CI: 1.10-2.71, respectively). High calcium levels were associated with a reduced risk for allograft loss. Results were even more pronounced for death-censored allograft loss. High concentrations of serum phosphate and CaPO(4) product were associated with an increased risk for allograft loss in these KTR, whereas high serum calcium concentrations seemed to lower the risk.

    View details for DOI 10.1111/j.1432-2277.2006.00436.x

    View details for Web of Science ID 000243975500005

    View details for PubMedID 17291218

  • Comparison of hemodialysis and peritoneal dialysis survival in The Netherlands KIDNEY INTERNATIONAL Liem, Y. S., Wong, J. B., Hunink, M. G., de Charro, F. T., Winkelmayer, W. C. 2007; 71 (2): 153-158

    Abstract

    Considerable geographic variation exists in the relative use of hemodialysis (HD) vs peritoneal dialysis (PD). Studies comparing survival between these modalities have yielded conflicting results. Our aim was to compare the survival of Dutch HD and PD patients. We developed Cox regression models using 16 643 patients from the Dutch End-Stage Renal Disease Registry (RENINE) adjusting for age, gender, primary renal disease, center of dialysis, year of start of renal replacement therapy, and included several interaction terms. We assumed definite treatment assignment at day 91 and performed an intention-to-treat analysis, censoring for transplantation. To account for time dependency, we stratified the analysis into three time periods, >3-6, >6-15, and >15 months. For the first period, the mortality hazard ratio (HR) of PD compared with HD patients was 0.26 (95% confidence interval (CI) 0.17-0.41) for 40-year-old non-diabetics, which increased with age and presence of diabetes to 0.95 (95% CI 0.64-1.39) for 70-year-old patients with diabetes as primary renal disease. The HRs of the second period were generally higher. After 15 months, the HR was 0.86 (95% CI 0.74-1.00) for 40-year-old non-diabetics and 1.42 (95% CI 1.23-1.65) for 70-year-old patients with diabetes as primary renal disease. We conclude that the survival advantage for Dutch PD compared with HD patients decreases over time, with age and in the presence of diabetes as primary disease.

    View details for DOI 10.1038/sj.ki.5002014

    View details for Web of Science ID 000243382300012

    View details for PubMedID 17136031

  • No associations between prolactin concentrations and response to erythropoiesis-stimulating agents in hemodialysis patients AMERICAN JOURNAL OF NEPHROLOGY Riegersperger, M., van Houte, M., Foedinger, M., Wojcik, J., Hoerl, W. H., Winkelmayer, W. C., Sunder-Plassmann, G. 2007; 27 (4): 390-396

    Abstract

    The effect of serum prolactin levels on the response to erythropoiesis-stimulating agents (ESA) in patients on chronic hemodialysis is unknown.We included 111 stable hemodialysis patients in this study and examined the association of serum prolactin concentrations with the response to ESA. Accordingly we implemented an ESA index as a measure of therapeutic efficacy. The two outcomes of this cohort study were the association of prolactin concentrations with response to ESA, both at baseline (cross-sectional component) and after 1-year of follow-up (prospective component), and the presence of macroprolactin.Two male patients, but none of the female patients, had serum prolactin concentrations within the reference range. Following precipitation with polyethylene glycol (PEG), 17 males (25.4%) and 9 females (20.6%) had serum prolactin concentrations within the reference range. Females had somewhat higher levels than males: 39.8 (IQR 32.3-64.5) versus 27.8 (IQR 23.4-47.8) ng/ml (p = 0.003). The ratio of prolactin(PEG)/prolactin(Native) was greater than 0.60 in 103 patients (92.8%), thus excluding significant amounts of macroprolactin. From uni- and multivariate analyses we did not find associations of serum prolactin concentrations with a response to ESA either at baseline or at follow-up.From this prospective study we provide evidence that elevated serum prolactin levels are not related to the presence of macroprolactin in chronic hemodialysis patients. Furthermore, serum prolactin concentrations are not associated with the response to erythropoietic therapy in these individuals.

    View details for DOI 10.1159/000104256

    View details for Web of Science ID 000247825400009

    View details for PubMedID 17587788

  • Strategies for the management of suspected heparin-induced thrombocytopenia - A cost-effectiveness analysis PHARMACOECONOMICS Patrick, A. R., Winkelmayer, W. C., Avorn, J., Fischer, M. A. 2007; 25 (11): 949-961

    Abstract

    Heparin-induced thrombocytopenia (HIT) is a rare but serious complication of heparin therapy. The diagnosis of HIT is difficult because its signs are non-specific and the heparin-platelet factor 4 (PF4) antibody test used to confirm the diagnosis is imprecise. Drugs used to treat HIT are costly and may carry an increased risk of bleeding.To evaluate the cost effectiveness, from a societal perspective, of four treatment approaches for patients with suspected HIT within a US critical care setting.A decision-tree was constructed for the management of a hypothetical cohort of critical care patients with possible evidence of HIT. The management strategies were: (i) no antibody testing, continue heparin (No Test and Wait); (ii) antibody testing, continue heparin while test results pending (Test and Wait); (iii) antibody testing and switch to a direct thrombin inhibitor (DTI) while test results pending (Test and Switch); and (iv) no antibody testing but switch to a DTI (No Test and Switch). We used argatroban as the DTI in our analysis. The outcomes were direct medical costs ($US; 2004 values), QALYs and incremental cost-effectiveness ratios (ICERs).Assuming an HIT prevalence of 3%, relative to less costly strategies, ordering an antibody test and switching patients to argatroban if the result was positive (Test and Wait) had an ICER of $US163 396/QALY. Pre-emptive switching to argatroban without antibody testing (No Test and Switch) was the most effective strategy but had an ICER of >$US1 million/QALY relative to the Test and Switch option. These results were highly sensitive to HIT prevalence among patients presenting with thrombocytopenia. Assuming a willingness to pay of $US50 000 per QALY, the Test and Wait strategy became cost effective when the prior probability of HIT was 8%. At a prior probability of 12%, Test and Switch was cost effective, and at probabilities of HIT in the 60-75% range, No Test and Switch was cost effective. In two-way analysis, the probability of developing a thrombotic event was a key driver of treatment choice at specific HIT probabilities.Testing for HIT in all typical critical care patients with thrombocytopenia is unlikely to represent a cost-effective management strategy. With increasing probability of HIT, strategies that include testing and a more rapid switch to a DTI appear more desirable. Accurate clinical judgment of the prior probability of HIT has a critical influence on the cost-effective management of HIT.

    View details for Web of Science ID 000251204500005

    View details for PubMedID 17960953

  • The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival TRANSPLANTATION Heinze, G., Collins, S., Benedict, M. A., Nguyen, L. L., Kramar, R., Winkelmayer, W. C., Haas, M., Kainz, A., Oberbauer, R. 2006; 82 (11): 1441-1448

    Abstract

    Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function.We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003. Actual and functional graft survival was compared between users and nonusers of ACEI/ARB using exposure propensity score models and time-dependent Cox regression models.Ten-year actual graft survival averaged 44% in the ACEI/ARB group, but only 32% in patients without ACEI/ARB (P=0.002). The hazard ratio of actual graft failure was 0.58 (95% confidence interval: 0.35-0.80, P=0.002) for ACEI/ARB users compared with nonconsumers. Seventy-one percent of subjects with ACEI/ARB had a functional graft at 10 years versus 64% of ACEI/ARB nonusers (P=0.027). The hazard ratio of functional graft loss was 0.48 (95% confidence interval: 0.24-0.91, P=0.025).Use of ACEI/ARB in patients experiencing delayed allograft function was associated with longer actual and functional transplant survival.

    View details for DOI 10.1097/01.tp.0000244587.74768.f7

    View details for Web of Science ID 000242948600013

    View details for PubMedID 17164715

  • A prospective study of anaemia and long-term outcomes in kidney transplant recipients NEPHROLOGY DIALYSIS TRANSPLANTATION Winkelmayer, W. C., Chandraker, A., Alan Brookhart, M., Kramar, R., Sunder-Plassmann, G. 2006; 21 (12): 3559-3566

    Abstract

    Anaemia is prevalent in kidney transplant recipients (KTR), and only few KTR with anaemia receive treatment with erythropoietin. Some have claimed that this undertreatment might contribute to suboptimal outcomes such as mortality and cardiovascular events in these patients. However, no evidence is currently available that anaemia is actually associated with such risks in KTR.We merged two cohorts of KTR to study the associations between anaemia and two outcomes: all-cause mortality and kidney allograft loss. Detailed information on the demographic and clinical characteristics of these 825 patients was available at baseline. As recommended by the American Society of Transplantation, anaemia was considered present if the haemoglobin concentration was < or =13 g/dl in men or < or =12 g/dl in women. Patients were followed using the Austrian Dialysis and Transplant Registry.After 8.2 years of follow-up, 251 patients died and 401 allografts were lost. In multivariate analyses, anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80-1.45), but it was associated with 25% greater risk of allograft loss (HR = 1.25; 95% CI: 1.02-1.59). This association was even more pronounced in death-censored analyses. Analyses using haemoglobin as a continuous variable or in categories also found no association with mortality.Anaemia may not be associated with mortality in KTR. In light of the recent findings of increased mortality in chronic kidney disease patients with higher haemoglobin treatment target, further evidence is needed to guide clinicians in the treatment of anaemia in these patients.

    View details for DOI 10.1093/ndt/gfl457

    View details for Web of Science ID 000242272800034

    View details for PubMedID 17040993

  • Angiotensin inhibition after myocardial infarction: Does drug class matter? JOURNAL OF GENERAL INTERNAL MEDICINE Winkelmayer, W. C., Fischer, M. A., Schneeweiss, S., Levin, R., Avorn, J. 2006; 21 (12): 1242-1247

    Abstract

    Angiotensin converting enzyme-inhibitors (ACEI) and angiotensin-II-receptor blockers (ARB) are equally efficacious in reducing mortality after MI, although the latter are far more costly. Little is known about their relative use after MI in typical care settings, and about their relative effectiveness outside the clinical trial setting.To assess temporal trends in the relative use of ACEI and ARB after myocardial infarction, and to test for differences in 1-year survival between users of these drug classes.Retrospective closed cohort study.Medicare beneficiaries who survived >90 days after myocardial infarction, had full prescription drug coverage, and who filled a prescription for either ACEI or ARB within 90 days of myocardial infarction.Relative use of ACEI versus ARB over time. Adjusted relative 1-year mortality between ACEI and ARB users.Between 1995 and 2004, 14,190 patients met inclusion criteria. Mean age was 80 years, 75% were female, and 90% were white. Overall, 88% received an ACEI, and 12% an ARB, with the proportion receiving an ARB increasing from 2% (1995) to 25% (2004; P<.001). Multivariate-adjusted 1-year mortality did not differ between ARB and ACEI users (HR: 1.04; 95% confidence interval: 0.88 to 1.22). The findings were similar for new users of ACEI/ARB, and for those with preexisting heart failure.ARB users had the same 1-year mortality after myocardial infarction as ACEI users in routine care. Use of more costly ARB has increased dramatically over time, to a quarter of ACEI/ARB users, despite the lack of a therapeutic advantage for most patients.

    View details for DOI 10.1111/j.1525-1497.2006.00590.x

    View details for Web of Science ID 000241675400009

    View details for PubMedID 17105523

  • Efficacy and safety of angiotensin II receptor blockade in elderly patients with diabetes DIABETES CARE Winkelmayer, W. C., Zhang, Z., Shahinfar, S., Cooper, M. E., Avorn, J., Brenner, B. M. 2006; 29 (10): 2210-2217

    Abstract

    While national guidelines recommend ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy in patients with diabetes and nephropathy, guidelines concerning elderly patients with diabetes have not endorsed these drugs. We sought to assess the nephroprotective efficacy and safety of ARB therapy in elderly patients by conducting age-specific subgroup analyses using data from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study.We studied 1,513 patients with type 2 diabetes and nephropathy who randomly received either losartan or placebo. We tested for effect modification by age of the effect of losartan on the incidence of the predefined end points (doubling of serum creatinine, end-stage renal disease [ESRD], or death) and the risk of adverse events.Of 1,513 participants, 421 (27.8%) were aged >65 years (maximum age 74 years). Age did not modify the efficacy of losartan in reducing the risk of the primary outcome, a composite of doubling of serum creatinine, ESRD, or death (P(interaction) = 0.66) or its individual components (all P(interaction) > 0.44). In patients aged >65 years, losartan reduced the risk of ESRD by 50% (95% CI 30-81, P = 0.005). We found no evidence that older patients were more likely to experience adverse events from losartan such as a rise in serum creatinine or hyperkalemia than younger patients.Elderly patients had the same level of benefits and risks as younger patients from treatment with losartan. Underuse of ACEI and ARB therapy in elderly patients because of the perceived lack of efficacy or a greater risk of adverse events appears unjustified.

    View details for DOI 10.2337/dc06-0570

    View details for Web of Science ID 000241013600005

    View details for PubMedID 17003295

  • Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation TRANSPLANT INTERNATIONAL Wong, W., Agrawal, N., Pascual, M., Anderson, D. C., Hirsch, H. H., Fujimoto, K., Cardarelli, F., Winkelmayer, W. C., Cosimi, A. B., Tolkoff-Rubin, N. 2006; 19 (8): 629-635

    Abstract

    Thymoglobulin is used effectively as an induction agent in kidney transplantation, but the optimal dose is not well established. We evaluated the degree and durability of T-cell clearances with two different thymoglobulin regimens in adult kidney transplant recipients (KTR). Seven KTR received a 3-day thymoglobulin-based induction of 1.0 mg/kg/day while nine received 1.5 mg/kg/day, in addition to maintenance immunosuppression. Lymphocyte subsets were monitored for 6 months. Renal function, infections and malignancies were monitored for 24 months. T-cell subsets were significantly lower by day 30 with the thymoglobulin 1.5 mg/kg/day regimen when compared with the 1.0 mg/kg/day regimen; this trend was sustained at 6-month (CD3(+): 438 +/- 254 vs. 1001 +/- 532 cells/mm(3), P = 0.016). Renal function between the two groups was not significantly different at 6- and 24-months post-transplant. One case of BK Virus viremia in the 1.5 mg/kg/day thymoglobulin group was detected. No acute rejection episodes, cytomegalovirus infections, or malignancies were noted in either group. Thymoglobulin induction was efficacious in both groups, but with a significantly sustained T-cell clearance in the 1.5 mg/kg/day regimen. A more profound T-cell clearance within the first 6 months postinduction therapy may translate into a decreased risk of immunological injury and improved long-term outcome after kidney transplantation.

    View details for DOI 10.1111/j.1432-2277.2006.00270.x

    View details for Web of Science ID 000238751000003

    View details for PubMedID 16827679

  • Surrogate markers in clinical studies: Problems solved or created? AMERICAN JOURNAL OF KIDNEY DISEASES Manns, B., Owen, W. F., Winkelmayer, W. C., Devereaux, P. J., Tonelli, M. 2006; 48 (1): 159-166

    View details for DOI 10.1053/j.ajkd.2006.03.044

    View details for Web of Science ID 000238826200020

    View details for PubMedID 16797400

  • Kidney function and use of recommended medications after myocardial infarction in elderly patients CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Charytan, D. M., Brookhart, M. A., Levin, R., Solomon, D. H., Avorn, J. 2006; 1 (4): 796-801

    Abstract

    Several studies have found reduced use of recommended medications after myocardial infarction (MI) in patients with impaired kidney function. However, the reasons for such undertreatment are not well understood. A total of 1380 Medicare patients who survived at least 90 d after MI and had prescription drug coverage through Pennsylvania's medication assistance program for the elderly were studied. Filled prescriptions were used to assess use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta blockers, and statins within 90 d of MI. Patients' demographics, comorbidities, and health care utilization before MI also were ascertained. We used logistic regression to test the association between kidney function and postdischarge use of each medication. Overall, 619 (45%) patients filled a prescription for a beta blocker, 675 (49%) received an ACEI or ARB, and 406 (29%) received a statin after discharge but within 90 d after their admission for MI. Reduced kidney function was associated with both lower beta blocker and statin use (P = 0.01 and P = 0.002, respectively), but after multivariate adjustment, these associations disappeared (P = 0.23 and P = 0.62, respectively). Use of ACEI or ARB was nearly half in patients with estimated GFR <30 ml/min compared with patients with better kidney function in univariate and multivariate analyses (P < 0.001). Analyses using serum creatinine measurements rather than estimations of GFR yielded similar results. Differences in other characteristics such as age, rather than kidney function, may be responsible for much or all the reported reduction in use of preventive medications after MI seen in patients with chronic kidney disease.

    View details for DOI 10.2215/CJN.00150106

    View details for Web of Science ID 000242241700026

    View details for PubMedID 17699289

  • Validity of International Classification of Diseases, Ninth Revision, Clinical Modification codes for acute renal failure JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Waikar, S. S., Wald, R., Chertow, G. M., Curhan, G. C., Winkelmayer, W. C., Liangos, O., Sosa, M., Jaber, B. L. 2006; 17 (6): 1688-1694

    Abstract

    Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

    View details for DOI 10.1681/ASN.2006010073

    View details for Web of Science ID 000237891100020

    View details for PubMedID 16641149

  • Caffeine and incident hypertension in women - Reply JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Winkelmayer, W. C., Curhan, G. C. 2006; 295 (18): 2137-2137
  • Associations between demographic factors and provider structures on cost and length of stay for hemodialysis patients with vascular access failure CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Brenner, L., Singh, A. K., Carnpbell, D., Frei, F., Winkelmayer, W. C. 2006; 1 (3): 455-461

    Abstract

    Vascular access failure (VAF) is a major determinant of morbidity and cost for hemodialysis patients, but little is known about the care patterns and cost implications that are associated with VAF. A total of 952 episodes of VAF in 348 patients were identified using specific procedure codes. Demographic and care pattern characteristics were available as were detailed costs for each episode. The determinants of several important performance measures were evaluated: Cost per episode, inpatient versus outpatient treatment, and length of stay (LOS). Over 5 yr of study, the proportion of VAF episodes that were treated on an outpatient basis increased from 31 to 63%. Average costs of outpatient versus inpatient episodes were $1491 and $8265, respectively. Men were more likely to be treated as outpatients (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.17 to 2.08), but once admitted, their LOS was longer (difference LOS +1.3; 95% CI +0.32 to +2.28) and more costly (delta$ +2603; 95% CI +632 to +4573). Nonblack, nonwhite patients were more likely to be treated as outpatients than were white patients (OR 2.07; 95% CI 1.27 to 3.36) and had shorter LOS once admitted (deltaLOS -2.37; 95% CI -4.23 to -0.49). Compared with Medicare, non-Medicare case-managed insurance was associated with a higher likelihood of outpatient treatment (OR 1.40; 95% CI 1.01 to 1.94) for VAF and shorter LOS (deltaLOS -1.36; 95% CI -2.48 to -0.24) and lower costs (delta$ -2742; 95% CI -5012 to -472) for inpatient treatment. It is concluded that gender and racial factors may influence VAF care. Over time, more VAF episodes are being treated in outpatient settings. Case management may lead to more outpatient treatment and shorter inpatient treatment of VAF.

    View details for DOI 10.2215/CJN.01401005

    View details for Web of Science ID 000242172900018

    View details for PubMedID 17699245

  • Assessing health state utilities in elderly patients at cardiovascular risk MEDICAL DECISION MAKING Winkelmayer, W. C., Benner, J. S., Glynn, R. J., Schneeweiss, S., Wang, P. S., Brookhart, M. A., Levin, R., Jackson, J. D., Avorn, J. 2006; 26 (3): 247-254

    Abstract

    Health state preferences can be a crucial component of cost-effectiveness analyses, but off-the-shelf health state utilities specifically for older people are not available.Among participants in PROSPER, a trial of pravastatin in patients>70 years, the authors assessed utilities for the health states that were relevant for the trial's cost-utility analysis. Subjects andThe authors cross-sectionally administered the Health Utilities Index, Mark 3 (HUI) to all PROSPER participants to assess each patient's health state at the time of interview; they then used the scale's multiattribute utility function to estimate the resulting utilities. The population was then stratified into 3 health states, and the mean utility function for each was calculated: recent myocardial infarction (MI, within 3 months), previous MI (>3 months), or no prior MI. Linear and logistic regression were used to control for potential demographic and clinical characteristics.Of the 5804 patients enrolled in the trial, 4677 were administered the HUI instrument. The likelihood of having a complete HUI response set decreased with higher age (P<0.001) but not with the other variables studied. A complete utility score could be calculated for 3390 participants. Of these, 2755 (81.3%) had no history of MI, 546 (16.1%) had an MI>3 months previously, and 89 (2.6%) had an MI within 3 months. The mean (median) utilities were virtually identical for these states: 0.75 (0.84), 0.74 (0.84), and 0.74 (0.84), respectively. From multivariate analyses, utilities decreased with higher age and the presence of several other comorbidities (diabetes, stroke, peripheral vascular disease); women had lower utilities than men (all P<0.01).In this large implementation of the HUI in elderly patients, the instrument did not detect any differences in estimated utilities related to having a MI. Potential causes of nondiscrimination for MI include the possibility that competing comorbidities may reduce the impact of MI on quality of life in this age group, as well as the possibility that a standard instrument derived from and validated in younger populations may not perform as well in elderly people.

    View details for DOI 10.1177/0272989X06288685

    View details for Web of Science ID 000237777900005

    View details for PubMedID 16751323

  • Predicting survival in patients requiring renal replacement therapy after cardiac surgery ANNALS OF THORACIC SURGERY Leacche, M., Winkelmayer, W. C., Paul, S., Lin, J., Unic, D., Rawn, J. D., Cohn, L. H., Byrne, J. G. 2006; 81 (4): 1385-1392

    Abstract

    We sought to develop and internally validate a prediction score for all-cause in-hospital mortality in patients who have acute renal failure and require renal replacement therapy after cardiac surgery.From January 1992 to July 2001, 136 of 14,000 patients (0.9%) had acute renal failure requiring renal replacement therapy after cardiac surgery. Multivariate logistic regression analysis, based on pre-renal replacement therapy variables, was used to construct a predictive score for all causes of in-hospital mortality. Subsequently, the score was validated in 27 patients who underwent surgery between August 2001 and March 2003.In-hospital mortality was 58% (79 of 136). From the logistic regression model, we assigned a score (range, 0 to 6) based on the presence of independent predictors of operative mortality (preoperative creatinine < or = 1.5 mg/dL [odds ratio (OR) = 5.0], hypertension [OR = 4.4], predialysis coma [OR = 9.6], sepsis [OR = 6.4], and total bilirubin > or = 2 mg/dL [OR = 5.6]). Higher scores strongly predicted mortality: patients who scored 3 or higher before the initiation dialysis (n = 54), had a mortality rate of 94% (51 of 54). In contrast, patients who scored 1 or less on this scale (n = 36), had a mortality of 16% (6 of 36). In the validation cohort, the sensitivity of the new score at the cutoff of 2 or fewer points versus 3 or more points was 0.71, the specificity was 0.90, the positive predictive value was 0.92, and the negative predictive value was 0.64.The prediction score represents a simple and accurate tool for predicting in-hospital mortality associated with renal replacement therapy for cardiac surgery patients before the institution of this resource-intensive treatment.

    View details for DOI 10.1016/j.athoracsur.2005.10.009

    View details for Web of Science ID 000236239200033

    View details for PubMedID 16564277

  • Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Heinze, G., Mitterbauer, C., Regele, H., Kramar, R., Winkelmayer, W. C., Curhan, G. C., Oberbauer, R. 2006; 17 (3): 889-899

    Abstract

    Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.

    View details for DOI 10.1681/ASN.2005090955

    View details for Web of Science ID 000242120400036

    View details for PubMedID 16481415

  • Incidence of end-stage renal disease in patients with type 1 diabetes was 7.8% at 30 years after diagnosis. ACP journal club Winkelmayer, W. C. 2006; 144 (2): 51-?

    View details for PubMedID 16539366

  • Prognostic associations between lipid markers and outcomes in kidney transplant recipients AMERICAN JOURNAL OF KIDNEY DISEASES Schaeffner, E. S., Fodinger, M., Kramar, R., Frei, U., Horl, W. H., Sunder-Plassmann, G., Winkelmayer, W. C. 2006; 47 (3): 509-517

    Abstract

    Hyperlipidemia is highly prevalent in kidney transplant recipients, but the prognostic significance for mortality and allograft survival in these patients has not been established sufficiently.We prospectively enrolled 733 kidney transplant recipients between 1996 and 1998. Clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplantation procedures and organ donor were obtained from the Eurotransplant Foundation database. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, independent relations of fasting plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels to risk for death from any cause and risk for kidney allograft loss were examined.During a median follow-up of 6.1 years, 154 patients died and 260 kidney allografts were lost. After careful multivariate adjustment, there were no significant associations between TG and TC levels and patient mortality. Patients in the highest quartile of TG and TC levels had no difference in risks for mortality compared with patients in the lowest quartile of these parameters (hazards ratio, 0.81; 95% confidence interval, 0.51 to 1.28; hazards ratio, 0.68; 95% confidence interval, 0.42 to 1.10, respectively). Similarly, no associations were found with allograft loss. Further analysis of associations between high-density lipoprotein cholesterol or low-density lipoprotein cholesterol categories and patient mortality or kidney allograft loss did not show associations.Elevated levels of TC or its subfractions and elevated TG levels are not associated with increased risk for patient mortality or allograft loss in these kidney transplant recipients.

    View details for DOI 10.1053/j.ajkd.2005.12.030

    View details for Web of Science ID 000236325700019

    View details for PubMedID 16490631

  • Endothelial progenitor cells in kidney transplant recipients TRANSPLANTATION Steiner, S., Winkelmayer, W. C., Kleinert, J., Grisar, J., Seldinger, D., Kopp, C. W., Watschinger, B., Minar, E., Horl, W. H., Fodinger, M., Sunder-Plassniann, G. 2006; 81 (4): 599-606

    Abstract

    Lower concentrations of endothelial progenitor cells (EPCs) may be associated with increased cardiovascular risk. EPC counts and their correlates have not yet been studied in kidney transplant recipients (KTR).We cross-sectionally studied EPC counts in 105 middle-aged KTR (mean estimated glomerular filtration rate 45.2 ml/min/1.73 m; range: 5.4 to 117.5). Using univariate and multivariate linear regression assuming a gamma distribution of the outcome, we examined the associations between counts of cultured EPCs and traditional cardiovascular disease risk factors (hypertension, diabetes, hyperlipidemia, smoking), kidney function, and immunosuppressive agents, amongst others.The median count of cultured EPCs was 34 cells per high-power field (interquartile range: 19 to 64), comparable to healthy individuals. From multivariate analyses, we found independent inverse associations between counts of cultured EPCs and body mass index, mean arterial pressure, and history of cardiovascular disease. Statin use was associated with greater EPC counts, whereas patients receiving azathioprine or angiotensin II receptor treatment had lower EPC counts (all P<0.01).This study suggests negative associations in KTR between EPC counts and body mass index, and blood pressure, whereas statin use was associated with greater EPC counts. These findings raise the hypothesis whether EPCs are responsible, at least in part, for the well established associations between these factors and cardiovascular outcomes in KTR.

    View details for DOI 10.1097/01.tp.0000198418.06383.e8

    View details for Web of Science ID 000235832900019

    View details for PubMedID 16495809

  • Poor short-term survival and low use of cardiovascular medications in elderly dialysis patients after acute myocardial infarction AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Charytan, D. M., Levin, R., Avorn, J. 2006; 47 (2): 301-308

    Abstract

    Beta-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) are standard therapies after myocardial infarction (MI) in the general population. Their use and association with mortality in elderly dialysis patients after MI have not been studied sufficiently.Claims records from Medicare and Medicaid patients aged 65 years and older who participated in prescription benefit plans of 2 eastern states were used to identify dialysis patients with MI between 1995 and 2003. Study outcomes were outpatient use of beta-blockers, statins, and ACE inhibitors and/or ARBs within 90 days after MI. We used multivariate logistic regression to assess predictors of such use. Multivariate Cox regression was applied to test for associations between beta-blocker, statin, and ACE-inhibitor and/or ARB use and 1-year mortality.We identified 902 dialysis patients who were hospitalized with MI. Of these, 39.5% died within 90 days and 63.6% died within 1 year after MI. Of 494 patients who were discharged within 21 days or less and survived longer than 90 days, 31.0% were administered an ACE inhibitor and/or ARB; 19.4%, a statin; and 34.2%, a beta-blocker after discharge. Use of ACE inhibitors and/or ARBs was associated with a 30% reduction in 1-year mortality (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50 to 0.98), whereas statin (HR, 0.97; 95% CI, 0.65 to 1.45) and beta-blocker use (HR, 1.05; 95% CI, 0.78 to 1.43) were not.Elderly dialysis patients have excessively high mortality and low use of standard therapies after MI. Only ACE inhibitors and/or ARBs were associated with a reduced risk for death at 1 year in this population. Whether the high mortality rate in this population is attributable to such low use of preventive cardiovascular medications remains uncertain.

    View details for DOI 10.1053/j.ajkd.2005.10.009

    View details for Web of Science ID 000235189300011

    View details for PubMedID 16431259

  • Genetic aspects of hyperhomocysteinemia in chronic kidney disease SEMINARS IN NEPHROLOGY Sunder-Plassmann, G., Winkelmayer, W. C., Fodinger, M. 2006; 26 (1): 8-13

    Abstract

    Patients with chronic kidney disease who are on dialysis or with a kidney transplant have higher total plasma homocysteine concentrations than individuals who are free from kidney disease. Several single-nucleotide polymorphisms of genes encoding enzymes that are involved in homocysteine metabolism have been studied in these patients. These polymorphisms are located in genes encoding of 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase, methionine synthase, cystathionine beta-synthase, glutamate carboxy peptidase II, reduced folate carrier 1, and transcobalamin II. Among the single-nucleotide polymorphisms studied, only MTHFR 677C>T was associated consistently with total plasma homocysteine levels, but there currently is no evidence of any association between MTHFR 677C>T genotype and long-term outcomes.

    View details for DOI 10.1016/j.semnephrol.2005.06.003

    View details for Web of Science ID 000235146600003

    View details for PubMedID 16412818

  • Cost-effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine therapy for blacks with heart failure CIRCULATION Angus, D. C., Linde-Zwirble, W. T., Tam, S. W., Ghali, J. K., Sabolinski, M. L., Villagra, V. G., Winkelmayer, W. C., Worcel, M. 2005; 112 (24): 3745-3753

    Abstract

    Fixed-dose combination of isosorbide dinitrate/hydralazine (ISDN/HYD) improved clinical outcomes in the African-American Heart Failure Trial (A-HeFT). We assessed the resource use, costs of care, and cost-effectiveness of ISDN/HYD therapy in the A-HeFT trial population.We obtained resource use data from A-HeFT, assigning costs through the use of US federal sources. Excluding indirect costs, we summarized the within-trial experience and modeled cost-effectiveness over extended time horizons, including a US societal lifetime reference case. During the mean trial follow-up of 12.8 months, the ISDN/HYD group incurred fewer heart failure-related hospitalizations (0.33 versus 0.47 per subject; P=0.002) and shorter mean hospital stays (6.7 versus 7.9 days; P=0.006). When study drug costs were excluded, both heart failure-related and total healthcare costs were lower in the ISDN/HYD group (mean per-subject heart failure-related costs, 5997 dollars versus 9144 dollars; P=0.04; mean per-subject total healthcare costs, 15,384 dollars versus 19,728 dollars; P=0.03). With an average daily drug cost of 6.38 dollars, ISDN/HYD therapy was dominant (reduced costs and improved outcomes) over the trial duration. Assuming that no additional benefits accrue beyond the trial, we project the cost-effectiveness of ISDN/HYD therapy using heart failure-related costs to be 16,600 dollars/life-year at 2 years after enrollment, 37,100 dollars/life-year at 5 years, and 41,800 dollars/life-year over lifetime (reference case).ISDN/HYD therapy, previously shown to improve clinical outcomes, also reduced resource use and costs in A-HeFT, primarily because of a large reduction in hospitalizations. Long-term use of ISDN/HYD therapy should be associated with a favorable cost-effectiveness profile in this population.

    View details for DOI 10.1161/CIRCULATIONAHA.105.563882

    View details for Web of Science ID 000233901500013

    View details for PubMedID 16344404

  • Underuse of ACE inhibitors and angiotensin II receptor blockers in elderly patients with diabetes AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Fischer, M. A., Schneeweiss, S., Wang, P. S., Levin, R., Avorn, J. 2005; 46 (6): 1080-1087

    Abstract

    National guidelines recommend angiotensin-converting enzyme (ACE)-inhibitor or angiotensin receptor blocker (ARB) therapy in patients with diabetes who also have hypertension and/or proteinuria to retard the progression of renal damage. However, little is known about the adequacy of adherence to these guidelines in elderly patients with diabetes and predictors of such appropriate ACE-inhibitor or ARB use.Using linked medical claims from Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly program, we studied a cohort of patients older than 65 years with diabetes. Baseline variables ascertained included age, sex, race, income, and several specific comorbid conditions. The outcome measure was at least 1 filled prescription for any ACE inhibitor or ARB during the quarter after the baseline year. We used multivariate logistic regression to measure predictors of use of the agents studied.Of 30,750 patients with diabetes studied, 21,138 patients (68.7%) also had hypertension and/or proteinuria. Of these, only 50.7% (95% confidence interval, 50.0 to 51.4) were administered an ACE inhibitor or ARB in the quarter studied. In multivariate analyses, failure to be administered either agent was associated significantly with older age, male sex, chronic lung disease, depression, dementia, and other mental illness. Greater rates of ACE-inhibitor or ARB use were found in patients with coronary artery disease or congestive heart failure.Only half the elderly patients with diabetes studied received recommended treatment with ACE inhibitors or ARBs. This shortfall could provide an opportunity for quality-improvement interventions that could result in important benefits in clinical outcomes for these high-risk patients.

    View details for DOI 10.1053/j.ajkd.2005.08.018

    View details for Web of Science ID 000233933600010

    View details for PubMedID 16310574

  • Effects of single-nucleotide polymorphisms in MTHFR and MTRR on mortality and allograft loss in kidney transplant recipients KIDNEY INTERNATIONAL Winkelmayer, W. C., Kramar, R., Sunder-Plassmann, G., Fodinger, M. 2005; 68 (6): 2857-2862

    Abstract

    Plasma total homocysteine (tHcy) is associated with cardiovascular outcomes in kidney transplant recipients (KTR). The methylenetetrahydrofolate-reductase (MTHFR) 677C>T polymorphism, an important determinant of plasma tHcy concentrations, could therefore constitute an important prognostic marker.We prospectively followed 710 KTR over >6 years. The MTHFR677C>T, MTHFR1298A>C, MTHFR1793G>A, and MTRR66A>G polymorphisms were analyzed. Demographic, clinical, and transplant-related information was obtained, and patients were followed-up using the Austrian Dialysis and Transplant Registry. Using Cox regression, we established the independent relations of each genotype to the risk of death from any cause, and/or kidney allograft loss.During a median follow-up of 6.1 years, 154 participants died and 260 kidney allografts were lost. Compared to patients with the MTHFR677CC genotype, patients with MTHFR677CT had an adjusted relative mortality risk of 1.02 (95%CI 0.70-1.47), and those with MTHFR677TT of 0.98 (95%CI 0.52-1.85). Compared to MTHFR677CC, the relative risks of kidney allograft loss were 0.93 (95%CI 0.70-1.23; MTHFR677CT) and 0.78 (95%CI 0.47-1.30; MTHFR677TT), respectively. None of the other genotypes were associated with the risks studied, either. These findings did not depend on whether we controlled for tHcy levels.This study does not support the routine use of MTHFR or MTRR genotyping for prognostic evaluation or risk-stratification in kidney transplant recipients.

    View details for Web of Science ID 000233204300043

    View details for PubMedID 16316363

  • Anaemia after renal transplantation EUROPEAN JOURNAL OF CLINICAL INVESTIGATION Lorenz, M., Winkelmayer, W. C., Horl, W. H., Sunder-Plassmann, G. 2005; 35: 89-94

    Abstract

    Anaemia is a frequent complication among long-term renal transplant recipients. A prevalence of approximately 40% has been reported in several studies. If renal function declines to stage 5 kidney disease, the prevalence of anaemia in kidney transplants is even higher. A positive correlation between haemoglobin concentration and creatinine clearance has been reported, which is a function of endogenous erythropoietin production by the functioning graft. Inflammation related to a retained kidney graft may cause hypo-responsiveness to erythropoietic agents once kidney transplant recipients return to dialysis. Furthermore, the use of azathioprine, mycophenolate mofetil and sirolimus may be associated with post-transplant anaemia. Along with erythropoietin deficiency, depletion of iron stores is one of the major reasons for anaemia in the kidney transplant population. The proportion of hypochromic red blood cells appears to be a useful parameter to measure iron supply and utilization as well as to estimate mortality risks in kidney transplant recipients. While anaemia is an important cardiovascular risk-factor after transplantation, our data suggest that anaemia is not associated with mortality and graft loss. Nevertheless, inadequate attention is paid so far to the management of anaemia after renal transplantation. A promising future aspect for risk reduction of cardiovascular disease includes the effect of erythropoietic agents on endothelial progenitor cells.

    View details for Web of Science ID 000234208500014

    View details for PubMedID 16281964

  • Habitual caffeine intake and the risk of hypertension in women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Winkelmayer, W. C., Stampfer, M. J., Willett, W. C., Curhan, G. C. 2005; 294 (18): 2330-2335

    Abstract

    Caffeine acutely increases blood pressure, but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain.To examine the association between caffeine intake and incident hypertension in women.Prospective cohort study conducted in the Nurses' Health Studies (NHSs) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years (1990-1991 to 2002-2003 questionnaires). Caffeine intake and possible confounders were ascertained from regularly administered questionnaires. We also tested the associations with types of caffeinated beverages.Incident physician-diagnosed hypertension.During follow-up, 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II. In both cohorts, no linear association between caffeine consumption and risk of incident hypertension was observed after multivariate adjustment (NHS I, P for trend = .29; NHS II, P for trend = .53). Using categorical analysis, an inverse U-shaped association between caffeine consumption and incident hypertension was found. Compared with participants in the lowest quintile of caffeine consumption, those in the third quintile had a 13% and 12% increased risk of hypertension, respectively (95% confidence interval in NHS I, 8%-18%; in NHS II, 6%-18%). When studying individual classes of caffeinated beverages, habitual coffee consumption was not associated with increased risk of hypertension. By contrast, consumption of cola beverages was associated with an increased risk of hypertension, independent of whether it was sugared or diet cola (P for trend <.001).No linear association between caffeine consumption and incident hypertension was found. Even though habitual coffee consumption was not associated with an increased risk of hypertension, consumption of sugared or diet cola was associated with it. Further research to elucidate the role of cola beverages in hypertension is warranted.

    View details for Web of Science ID 000233089700025

    View details for PubMedID 16278361

  • Long-term patient and graft survival in the eurotransplant senior program: A single-center experience TRANSPLANTATION Fabrizii, V., Kovarik, J., Bodingbauer, M., Kramar, R., Horl, W. H., Winkelmayer, W. C. 2005; 80 (5): 582-589

    Abstract

    The Eurotransplant Senior Program (ESP) was launched in 1999, targeted to increase the supply of donor kidneys to the elderly. This program requires local allocation of kidneys from cadaveric donors >65 years to recipients >65 years.Of all patients >65 years who received a kidney transplant in 1999-2002 at our center, 59 patients were transplanted through the ESP protocol (ESP group), and 44 patients received a transplant from a younger donor (EuroTransplant Kidney Allocation System, ETKAS group). Recipients were followed for up to 5.3 years using the Austrian Dialysis and Transplant Registry. Outcomes studied included all-cause mortality and allograft loss.Age, sex, and comorbid conditions did not differ by group. Donor age was higher (69 vs. 36 years; P < 0.001) and cold ischemia time shorter in the ESP group (10 vs. 15 hr; P < 0.001). Number of HLA mismatches was greater in the ESP group (3.8 vs. 3.0; P = 0.003). ESP patients were more likely to receive induction therapy and less likely to receive cyclosporine A. Primary nonfunction, delayed graft function, operative mortality, rate of acute rejection episodes, and length of stay did not differ by group. Although serum creatinine at discharge was higher in ESP patients (1.7 vs. 1.4 mg/dL; P < 0.001), 4-year mortality (hazard ratio [HR] = 0.68; 95% CI: 0.31-1.49) and graft loss (HR = 0.61; 95% CI: 0.29-1.28) tended to be less.Long-term patient and graft survival were comparable between elderly patients who received their organ via the ESP and the regular ETKAS algorithm.

    View details for DOI 10.1097/01.tp.0000168340.05714.99

    View details for Web of Science ID 000232127200006

    View details for PubMedID 16177629

  • The hepatotoxicity of antifungal medications in bone marrow transplant recipients CLINICAL INFECTIOUS DISEASES Fischer, M. A., Winkelmayer, W. C., Rubin, R. H., Avorn, J. 2005; 41 (3): 301-307

    Abstract

    Systemic antifungal medications can be lifesaving but can also have important toxicities. With a number of new antifungal drugs being introduced, there is a compelling need to define the toxicities associated with existing therapies.We identified cases of hepatotoxicity among patients who underwent bone marrow transplantation and selected matched control subjects from the same population. Multivariable logistic regression modeling was used to control for patient characteristics in evaluating the relationship between hepatotoxicity and exposure to antifungal medications. Follow-up analyses were performed for patients who continued receiving antifungal medications after developing hepatotoxicity.The unadjusted incidence of hepatotoxicity was 0.78 cases per 100 patient-days of exposure to amphotericin deoxycholate, 0.98 for fluconazole, and 1.50 for liposomal amphotericin B. Case-control analyses found that liposomal amphotericin B was associated with a substantial increase in the risk of hepatotoxicity in these patients (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.61-6.88); a smaller increase in risk was found for fluconazole (OR, 1.99; 95% CI, 1.21-3.26). There was no statistically significant association between amphotericin B deoxycholate and the development of hepatotoxicity. Patients had greater elevations of serum transaminase values associated with exposure to larger cumulative doses of liposomal amphotericin B. In the follow-up analysis of patients who developed hepatotoxicity and who continued receiving antifungal medication, one-third of those receiving liposomal amphotericin B had marked increases in bilirubin levels, as opposed to 8% of patients treated with fluconazole.In these bone marrow transplant recipients, liposomal amphotericin B and fluconazole were both associated with increased risk of hepatotoxicity, independent of other treatments received or patient characteristics; the magnitude of the risk was larger for liposomal amphotericin B. Patients who develop hepatotoxicity appear to tolerate continued therapy with fluconazole, but a large fraction of those who received liposomal amphotericin B have worsening conditions with continued treatment.

    View details for Web of Science ID 000230305300004

    View details for PubMedID 16007524

  • Identification of individuals with CKD from medicare claims data: A validation study AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Schneeweiss, S., Mogun, H., Patrick, A. R., Avorn, J., Solomon, D. H. 2005; 46 (2): 225-232

    Abstract

    Medicare claims data might provide an efficient source for outcomes research in patients with chronic kidney disease (CKD). However, in the absence of laboratory data, one would need to identify patients with CKD from diagnosis codes associated with health care claims. The validity of this approach to identify patients with CKD has not been sufficiently studied.From chart abstraction, we obtained the first serum creatinine measurement of 1,852 elderly Medicare beneficiaries upon hospitalization for myocardial infarction and estimated each patient's glomerular filtration rate. We then searched all Medicare claims of the preceding year for the presence of a diagnosis code for diabetic nephropathy, hypertensive nephropathy, chronic renal insufficiency, acute renal failure, and miscellaneous other renal diseases. Using the gold standard of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (<1.00 mL/s/1.73 m2) for definition of CKD, we calculated the sensitivity, specificity, and positive and negative predictive values for each of these diagnoses and combinations of these diagnoses.The sensitivity of individual diagnosis algorithms ranged from 2.7% for diabetic nephropathy to 17.5% for miscellaneous. However, miscellaneous had a lower specificity (95.5%) than all other individual diagnosis algorithms (all > or =99%). Using combinations of these algorithms improved sensitivity up to 26.6%, but at the cost of lower specificity. Positive predictive values generally were high (85.7% to 97.5%), but negative predictive values were low (32.4% to 37.4%). Conclusion: High positive predictive values indicate that Medicare claims data can be used to accurately identify patients with CKD for study. However, the utility of such databases for comparison of patients with CKD versus lesser degrees of CKD is limited.

    View details for DOI 10.1053/j.ajkd.2005.04.029

    View details for Web of Science ID 000230926100005

    View details for PubMedID 16112040

  • A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors HAEMOPHILIA Putnam, K. G., Bohn, R. L., Ewenstein, B. M., Winkelmayer, W. C., Avorn, J. 2005; 11 (3): 261-269

    Abstract

    Treatment of acute bleeding episodes in patients with haemophilia A and inhibitory antibodies to factor VIII (FVIII) most often involves the use of bypassing haemostatic agents, such as activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa). We constructed a cost minimization model to compare the costs of initial treatment with aPCC vs. rFVIIa in the home treatment of minor bleeding episodes. We developed a clinical scenario describing such a case and presented it to a panel of US haemophilia specialists. For each product class, we asked panellists to provide dosing regimens required to achieve complete resolution of a minor haemarthrosis in a child with high-titre inhibitors, and for the probabilities of success at two time points (8-12 and 24 h). Consensus among the panellists was refined by a second round of the process, and the median values resulting were used as inputs to a decision analysis model. Sensitivity analyses were conducted to determine threshold values for key variables. The base case model found that initial treatment with aPCC would result in a mean cost per episode of 21 000 dollars, compared with 33 400 dollars for initial treatment with rFVIIa. Sensitivity analyses over a range of clinically plausible values for cost, dosing, and efficacy did not change the selection of aPCC as the dominant strategy.

    View details for DOI 10.1111/j.1365-2516.2005.01098.x

    View details for Web of Science ID 000228979800010

    View details for PubMedID 15876272

  • Associations between MTHFR 1793G > A and plasma total homocysteine, folate, and vitamin B-12 in kidney transplant recipients KIDNEY INTERNATIONAL Winkelmayer, W. C., Huber, A., Wagner, O. F., Horl, W. H., Sunder-Plassmann, G., Fodinger, M. 2005; 67 (5): 1980-1985

    Abstract

    Currently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B(12), folate, or total homocysteine (tHcy).In a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B(12), folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.The allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N= 72) or homozygosity (N= 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B(12) (P= 0.33) or tHcy (P= 0.70), but a borderline association with higher folate concentrations was detected (Deltafolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P= 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B(12) concentrations.Higher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B(12) in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes.

    View details for Web of Science ID 000228582900044

    View details for PubMedID 15840047

  • Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: A prospective study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Kramar, R., Curhan, G. C., Chandraker, A., Endler, G., Fodinger, M., Horl, W. H., Sunder-Plassmann, G. 2005; 16 (1): 255-260

    Abstract

    Homocysteine is implicated to be an atherogenic amino acid and has been associated with increased risk of adverse cardiovascular outcomes. The prognostic significance of plasma total homocysteine (tHcy) levels for mortality and allograft loss in kidney transplant recipients has not been established. A total of 733 kidney transplant recipients who were seen for a routine visit at this transplant clinic in 1996 to 1998 were studied prospectively. During that visit, clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplant procedure and the organ donor was obtained from the Eurotransplant Foundation database. Patients were followed prospectively using the Austrian Dialysis and Transplant Registry. With the use of proportional-hazards regression, the independent relations of fasting plasma tHcy levels to the risk of death from any cause and kidney allograft loss were examined. During a median follow-up of 6.1 yr, 154 participants died and 260 kidney allografts were lost. After adjustment for several important risk factors, elevated tHcy levels (>/=12 micromol/L) were associated with 2.44 times the mortality risk of patients with normal tHcy levels (hazards ratio 2.44; 95% confidence interval 1.45 to 4.12; P < 0.001). Similarly, elevated tHcy levels were associated with 1.63 times increased risk of kidney allograft loss (hazards ratio 1.63; 95% confidence interval 1.09 to 2.44; P = 0.02). In this single-center sample, baseline fasting plasma tHcy levels were independently associated with the risk of death and kidney allograft loss. The clinical utility of homocysteine-lowering therapy, such as multivitamin therapy, to reduce the rates of these end points needs to be studied.

    View details for Web of Science ID 000226008700034

    View details for PubMedID 15563562

  • Comparing the costs, risks, and benefits of competing strategies for the primary prevention of venous thromboembolism. Circulation Avorn, J., Winkelmayer, W. C. 2004; 110 (24): IV25-32

    Abstract

    Systematic cost-effectiveness analyses of regimens used for preventing venous thromboembolism (VTE) are becoming increasingly important for several reasons: the aging of the population, with an accompanying increase in admissions for orthopedic procedures or other surgery; expanded indications for thromboprophylaxis in nonsurgical patients; and the introduction of more expensive new agents that may increase safety and efficacy. At the same time, health care systems are under unprecedented pressure to contain the costs of care, particularly medications. Such economic analyses are made more difficult by the paucity of clinical trials comparing treatment regimens to one another rather than to placebo. Several methodological issues must be kept in mind when evaluating cost-effectiveness analyses of VTE prophylaxis. These include the perspective from which the analysis is performed (eg, the health care system as a whole versus a particular payer), limitations of trial data (eg, artificially short time horizons), and definition of outcomes (eg, flawed definition and grouping together of adverse effects or treatment failures). Quantifying costs across nations and health care systems is problematic as well. Another challenge is the extrapolation of efficacy data from highly monitored study patients to routine practice settings. Nevertheless, cost-effectiveness analyses of VTE treatments conducted in orthopedic surgery, trauma, general surgery, and acute medical settings can help define the relationships among expenditures, adverse outcomes, and patient benefit for particular therapeutic strategies in a variety of clinical situations.

    View details for PubMedID 15598645

  • Comparing the costs, risks, and benefits of competing strategies for the primary prevention of venous thromboembolism CIRCULATION Avorn, J., Winkelmayer, W. C. 2004; 110 (24): 25-32
  • Percentage of hypochromic red blood cells is an independent risk factor for mortality in kidney transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Winkelmayer, W. C., Lorenz, M., Kramar, R., Horl, W. H., Sunder-Plassmann, G. 2004; 4 (12): 2075-2081

    Abstract

    There are no published studies on the associations between anemia or iron status parameters and important long-term outcomes in kidney transplant recipients (KTR). We prospectively studied 438 KTR from a large transplant clinic for all-cause mortality and kidney allograft loss. Hemoglobin and iron status parameters (serum iron, transferrin, transferrin saturation, ferritin, percentage of hypochromic red blood cells [%HRBC]) were assessed at baseline as were important demographic, clinical and laboratory characteristics. The Austrian Dialysis and Transplant Registry and the Eurotransplant database were used to ascertain immunological and transplantation-related parameters and to ascertain death and allograft rejection. Cox proportional hazard models were used for analyses. Over 7.8 years of follow-up, 129 deaths (29.5%) occurred and 208 grafts (47.5%) were lost. From multivariate analyses, we found that anemia (hemoglobin <10g/dL) was not associated with mortality or graft loss. Among the iron status parameters, only %HRBC was associated with greater all-cause mortality. Patients with HRBC >10% had twice the mortality risk (HR: 2.06; 95%CI: 1.12-3.79) compared to patients with HRBC <5%. Neither of the iron status parameters were associated with allograft rejection. In conclusion, we found that %HRBC was an independent risk factor for mortality in KTR, while other iron status parameters or anemia were not associated with risk. Larger studies on the association between anemia and these outcomes are warranted.

    View details for DOI 10.1111/j.1600-6143.2004.00604.x

    View details for Web of Science ID 000225487400022

    View details for PubMedID 15575912

  • Regarding impact of epoetin alfa on clinical end points in patients with chronic renal failure: A meta-analysis KIDNEY INTERNATIONAL Tonelli, M., Owen, W. F., Jindal, K., Winkelmayer, W. C., Manns, B. 2004; 66 (4): 1712-1712

    View details for Web of Science ID 000223821000051

    View details for PubMedID 15458473

  • A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States KIDNEY INTERNATIONAL Manns, B., Stevens, L., Miskulin, D., Owen, W. F., Winkelmayer, W. C., Tonelli, M. 2004; 66 (3): 1239-1247

    Abstract

    The Kidney Disease Outcomes Quality Initiatives (K/DOQI) guidelines on bone metabolism and disease in chronic kidney disease were recently published. Despite limited evidence of clinical effectiveness and without detailed consideration of cost, these guidelines recommend the use of a nonmineral-containing phosphate binder (i.e., sevelamer) in several common clinical situations. The objective of this study is to use the example of sevelamer to outline the information that is needed to assist health care payers with the decision to fund a new and expensive therapy.We assessed the clinical benefit of sevelamer by performing a systematic review of all randomized trials evaluating its use. To estimate the direct budget impact associated with implementation of the K/DOQI bone disease guidelines, we used laboratory and medication data available from two cohorts of dialysis patients (one treated in Canada and one in the United States) to determine the proportion of patients who meet the criteria for the use of sevelamer as described in the K/DOQI bone disease guidelines.No randomized trials document the impact of sevelamer on survival, hospitalization, or quality of life. However, at least 51% and 64% of dialysis patients in the Canadian and American cohorts, respectively, would meet K/DOQI criteria for use of sevelamer. Extrapolating to the United States dialysis population, adoption of the K/DOQI bone guidelines would result in expenditures of approximately 781 million dollars annually on sevelamer alone.Given their potential budgetary impact, future nephrology clinical practice guidelines should consider resource use, in addition to clinical data.

    View details for Web of Science ID 000223217700049

    View details for PubMedID 15327423

  • Patterns of co-occurrence of three single nucleotide polymorphisms of the 5,10-methylenetetrahydrofolate reductase gene in kidney transplant recipients EUROPEAN JOURNAL OF CLINICAL INVESTIGATION Winkelmayer, W. C., Sunder-Plassmann, G., Huber, A., Fodinger, M. 2004; 34 (9): 613-618

    Abstract

    Recently, a new mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) encoding gene was first described (1793G > A). Only few reports have studied the prevalence of this polymorphism, especially in combination with other MTHFR mutations (677C > T, 1298A > C).We cross-sectionally identified the novel MTHFR 1793G > A polymorphism in 730 kidney transplant recipients. MTHFR 677C > T and 1298A > C were also assessed and the frequency of each was described individually as well as in cross-tabulation with the other MTHFR genotypes. The expected number of patients for each MTHFR genotype combination was calculated and contrasted with the observed numbers. Fisher's exact test was used for statistical inference.The allelic frequency of MTHFR 1793G > A was 0.052. Seventy-two patients (9.9%) were heterozygous and two patients (0.3%) were homozygous. From the cross-tabulations, we identified 53 patients (expected: 33.6) with the MTHFR 1298AC/1793GA genotype and 17 patients (expected: 6.7) with the MTHFR 1298CC/1793GA genotype. Furthermore, we found two patients with double homozygosity for MTHFR 1793G > A and MTHFR 1298A > C (MTHFR 1793AA/1298CC genotype). The frequencies of these genotype combinations were substantially larger than could be expected (P < 0.001).These findings suggest a selection or survival advantage for individuals with combined MTHFR 1793G > A and MTHFR 1298A > C genotypes, possibly owing to a mutually stabilizing effect on MTHFR enzyme activity.

    View details for Web of Science ID 000223996500005

    View details for PubMedID 15379760

  • Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction CLINICAL TRANSPLANTATION Wong, W. C., Tolkoff-Rubin, N., Delmonico, F. L., Cardarelli, F., Saidman, S. L., Farrell, M. L., Shih, V., Winkelmayer, W. C., Cosimi, A. B., Pascual, M. 2004; 18 (4): 341-348

    Abstract

    Long-term use of cyclosporine (CsA) contributes to post-transplant cardiovascular disease (CVD). Hence, a reduction in CsA dosage in kidney transplant recipients (KTR) may improve long-term outcomes. We analyzed the effects of 50% CsA dose reduction on the CVD risk profile in stable KTR.Thirty-one KTR on a regimen of CsA, prednisone and mycophenolate mofetil (MMF) were studied. Patients were randomized to either a) continue their previously determined CsA dose (control group, n = 15) or b) lower their CsA dose by 50% (CsA reduction group, n = 16). Renal function, blood pressure, lipid profile, plasma homocysteine (HCY), C-reactive protein (CRP), fibrinogen, and uric acid were compared at baseline and at 6 months.At 6 months, there was a significant improvement in allograft function, systolic blood pressure, number of anti-hypertensive medications and serum uric acid levels in the CsA reduction group. No significant decrease in plasma HCY, CRP, fibrinogen or improvement in lipid profile was found. In contrast, in the Control group, there was a significant increase in HCY, uric acid, and triglycerides. No acute rejection occurred in either group.A greater reduction in CsA dose could further improve CVD risk profiles, although this may increase the risk of acute or subclinical rejection.

    View details for DOI 10.1111/j.1399-0012.2004.00171.x

    View details for Web of Science ID 000222418600001

    View details for PubMedID 15233807

  • Propensity scores: help or hype? NEPHROLOGY DIALYSIS TRANSPLANTATION Winkelmayer, W. C., Kurth, T. 2004; 19 (7): 1671-1673

    View details for DOI 10.1093/ndt/gfh104

    View details for Web of Science ID 000222530500001

    View details for PubMedID 15069182

  • Hydroxyethyl starch-induced postoperative bleeding in cardiac surgery patients - More trials needed? Reply CHEST Avorn, J., Winkelmayer, W. 2004; 126 (1): 312-312
  • C-reactive protein and body mass index independently predict mortality in kidney transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Winkelmayer, W. C., Lorenz, M., Kramar, R., Fodinger, M., Horl, W. H., Sunder-Plassmann, G. 2004; 4 (7): 1148-1154

    Abstract

    C-reactive protein (CRP) is a risk factor for cardiovascular outcomes and mortality in the general population. To date, there are no prospective studies of the association between CRP and mortality or allograft loss in kidney transplant recipients (KTR). In 1995, 438 consecutive KTR were enrolled in this prospective study. Important information on demographic, clinical and immunological characteristics was collected at baseline, and CRP was measured using standard methods. Patients were then followed-up for a median 7.8 years. Time-to-event analyses (univariate and multivariate Cox proportional hazards regression models) were used to study the main outcomes: all-cause mortality and kidney allograft loss, defined as the earlier of return to dialysis, re-transplantation, or death. From univariate analyses, we found that CRP >or=0.5 mg/dL was associated with a 83% greater mortality risk compared with lower levels of this inflammatory marker [hazard ratio (HR) = 1.83; 95% confidence interval (CI): 1.23-2.72; p = 0.003]. After multivariate adjustment, patients with a CRP >or=0.5 mg/dL had a 53% higher mortality risk compared with patients whose CRP was below that threshold (HR = 1.53; 95% CI: 1.01-2.31; p = 0.04). No associations between CRP and the risk of kidney allograft loss were detected. Furthermore, we were not able to detect any effect modification between CRP and body mass index on the outcomes under study. We conclude that CRP predicts all-cause mortality, but not allograft loss in stable KTR.

    View details for DOI 10.1111/j.1600-6143.2004.00477.x

    View details for Web of Science ID 000221968700020

    View details for PubMedID 15196074

  • Knowledge and attitude regarding organ donation among medical students and physicians TRANSPLANTATION Schaeffner, E. S., Windisch, W., Freidel, K., Breitenfeldt, K., Winkelmayer, W. C. 2004; 77 (11): 1714-1718

    Abstract

    There is a discrepancy between demand and supply of donor organs for kidney transplantation. Health care providers can influence the willingness to donate or hold an organ donor card. It is unclear how educated current and future health care professionals are about organ donation and what constitutes their attitude toward this topic.The authors conducted a cross-sectional survey among 1136 medical students and physicians to evaluate the knowledge about and attitude toward organ donation and transplantation at a large academic medical center in Germany. The authors used a 28-item questionnaire that included items on knowledge, attitude, and demographics.Only 8% of the respondents felt sufficiently prepared for approaching relatives of potential organ donors. Knowledge about and attitude toward organ donation were highly associated with increasing level of medical education. In multivariate analyses, knowledge (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.08-1.25), attitude (OR, 1.03; 95% CI, 1.02-1.04), and level of education (OR for preclinical students, 0.39; 95% CI, 0.20-0.76 compared with physicians) were significantly associated with the likelihood of holding an organ donor card, whereas age, gender, and personal experience with renal replacement therapy were not.Higher medical education is associated with greater knowledge about and a more positive attitude toward organ donation. Health care professionals with a higher education level are more likely to hold an organ donor card and also feel more comfortable in approaching relatives of potential organ donors. Educating health care professionals about the organ donation process appears to be an important factor in maximizing the benefits from the limited organ donor pool.

    View details for Web of Science ID 000222094300015

    View details for PubMedID 15201671

  • Methionine synthase reductase MTRR 66A > G has no effect on total homocysteine, folate, and vitamin B-12 concentrations in renal transplant patients ATHEROSCLEROSIS Feix, A., Winkelmayer, W. C., Eberle, C., Sunder-Plassmann, G., Fodinger, M. 2004; 174 (1): 43-48

    Abstract

    The association of variants of the gene encoding methionine synthase reductase (MTRR) with hyperhomocysteinemia, folate and Vitamin B(12) status in kidney graft recipients is unknown. We examined two mutations in MTRR in a cross-sectional study of 733 kidney graft recipients. The allele frequency of MTRR 66G was 0.55. 369 patients (50.3%) were heterozygous and 219 patients (29.9%) were homozygous for the mutation. None of the patients showed the 997C > G mutation. The allelic variants of MTRR 66A > G showed no significant association with total homocysteine (tHcy) levels, both in univariate analyses, and in a multivariate model controlling for age, gender, body mass index, renal function, time since transplantation, underlying kidney disease, as well as the MTHFR 677C > T/1298A > C genotypes. Similarly, no significant associations between the MTRR 66A > Ggenotypes and plasma folate or Vitamin B(12) levels were found. In conclusion, MTRR 66A > G has no major effect on tHcy, folate, or Vitamin B(12) plasma concentrations in kidney graft recipients.

    View details for DOI 10.1016/j.atherosclerosis.2003.12.036

    View details for Web of Science ID 000221673700006

    View details for PubMedID 15135249

  • Effects of TCN2 776C > G on vitamin B-12, folate, and total homocysteine levels in kidney transplant patients KIDNEY INTERNATIONAL Winkelmayer, W. C., Skoupy, S., Eberle, C., Fodinger, M., Sunder-Plassmann, G. 2004; 65 (5): 1877-1881

    Abstract

    Controversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B(12), folate, or total homocysteine.In a cross-sectional study of 732 kidney allograft recipients, patients were categorized by TCN2 776C>G genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B(12), folate, and total homocysteine plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of the TCN2 776C>G gene and these three dependent variables.The allele frequency for TCN2 776C>G was 0.46. Heterozygosity or homozygosity for TCN2 776C>G was not associated with plasma levels of vitamin B(12) (776CG, P= 0.22; 776GG, P= 0.89), folate (776CG, P= 0.91; 776GG, P= 0.84), or total homocysteine (776CG, P= 0.11; 776GG, P= 0.33) even after adjustment for several possible confounders.We conclude from this largest study on the subject thus far that there are no associations between allelic variants of TCN2 776C>G and plasma vitamin B(12), folate, or total homocysteine plasma levels in kidney transplant patients.

    View details for Web of Science ID 000221020900050

    View details for PubMedID 15086930

  • Pharmacoepidemiology of anemia in kidney transplant recipients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Kewalramani, R., Rutstein, M., Gabardi, S., Vonvisger, T., Chandraker, A. 2004; 15 (5): 1347-1352

    Abstract

    ABSTRACT. Anemia has long been known to be a complication of end-stage renal disease (ESRD), and it has been linked to cardiovascular morbidity and mortality. Although kidney transplant recipients (KTR) are prone to experiencing cardiovascular outcomes, little is known about the epidemiology of anemia in this population. With few exceptions, studies to date have not fully evaluated the associations between posttransplant anemia (PTA) and medications commonly used in KTR, particularly immunosuppressant drugs, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). The authors aimed to specifically investigate possible associations between these drugs and PTA. Detailed medical information was retrospectively collected on 374 consecutive KTR from our transplant clinic. Univariate/multivariate linear regression models were used to test for associations between hematocrit (HCT) and other covariates, and logistic regression models were used to detect independent predictors of PTA, defined as HCT <33%. The mean time since transplantation was 7.7 yr, and mean creatinine was 2.2 mg/dl. The prevalence of PTA was 28.6%. Ten percent of all patients were on erythropoietin therapy, but only 41.6% of patients whose HCT was <30 received this treatment. From multivariate analyses, the authors found that female gender and lower renal function were associated with lower HCT (both P < 0.001). Patients on ACEI had significantly lower HCT (P = 0.005) compared with patients without such treatment. In addition, a significant curvilinear dose-response relationship was found between ACEI dose and HCT. Among the immunosuppressant drugs, mycophenolate mofetil (P = 0.05) and tacrolimus (P = 0.02) were associated with a lower HCT. The authors conclude that PTA is prevalent and undertreated in KTR. Several medications that are possibly modifiable correlates of PTR deserve further study.

    View details for DOI 10.1097/01.ASN.0000125551.59739.2E

    View details for Web of Science ID 000221043000030

    View details for PubMedID 15100376

  • Patient and graft survival in older kidney transplant recipients: Does age matter? JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Fabrizii, V., Winkelmayer, W. C., Klauser, R., Kletzmayr, J., Saemann, M. D., Steininger, R., Kramar, R., Horl, W. H., Kovarik, J. 2004; 15 (4): 1052-1060

    Abstract

    An increasing gap between supply and demand of donor kidneys for transplantation exists. There is concern regarding the allocation of scarce organs to elderly patients, because the benefit obtained by the transplant may be less in elderly compared with younger recipients. It was the objective of this study to determine differences in patient and organ survival between organ recipients >65 yr and 50 to 64 yr of age at transplantation. A retrospective cohort of 627 patients >50 yr who received a kidney transplant between 1993 and 2000 was assembled. Detailed information on patient demographics, comorbidities, and immunological and donor characteristics was ascertained before transplantation. Five-year patient and graft survival were evaluated by Kaplan-Meier survival curves and multivariate Cox proportional-hazard models. Five-year patient mortality was similar between patients aged >65 and 60 to 64 at transplantation (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.66 to 1.74). Patients aged 50 to 59 yr showed a clear trend toward lower 5-yr mortality (RR = 0.66; 95% CI, 0.43 to 1.03). Compared with patients >65 yr, 5-yr graft loss was not different in patients aged 60 to 64 (RR = 1.28; 95% CI, 0.82 to 2.02) or those aged 50 to 59 yr at transplantation (RR = 1.02; 95% CI, 0.68 to 1.53). After thorough control for confounding, 5-yr graft survival was not materially different by age group. Discrimination against older candidates for kidney transplantation on age-related grounds alone is not warranted.

    View details for DOI 10.1097/01.ASN.0000120370.35927.40

    View details for Web of Science ID 000220316900025

    View details for PubMedID 15034109

  • Stable creatinine clearance using large-dose HES versus reduced GFR - Reply KIDNEY INTERNATIONAL Winkelmayer, W. C., Avorn, J. 2004; 65 (3): 1111-1112
  • How well do patients report noncompliance with antihypertensive medications? a comparison of self-report versus filled prescriptions PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Wang, P. S., Benner, J. S., Glynn, R. J., Winkelmayer, W. C., Mogun, H., Avorn, J. 2004; 13 (1): 11-19

    Abstract

    To address poor patient compliance with antihypertensives, clinicians and researchers need accurate measures of adherence with prescribed regimens. Although self-reports are often the only means available in routine practice, their accuracy and agreement with other data sources remain questionable.A telephone survey was conducted on 200 hypertensive patients treated with a single antihypertensive agent in a large health maintenance organization (HMO) or a Veterans Affairs medical center (VAMC) to obtain self-reports of the frequency of missing antihypertensive therapy. We then analyzed records of all filled prescriptions to calculate the number of days that patients actually had antihypertensive medications available for use. Agreement between the two data sources was measured with correlation coefficients and kappa statistics. Logistic regression models were used to identify demographic, clinical and psychosocial correlates of overstating compliance.There was very poor agreement between self-reported compliance and days actually covered by filled prescriptions (Spearman correlation coefficient = 0.15; 95%CI: 0.01, 0.28). Very poor agreement was also observed between a categorical measure of self-reported compliance (ever vs. never missing a dose) and categories of actual compliance defined by filled prescriptions (< 80% vs > 80% of days covered; kappa = 0.12, 95%CI: -0.02, 0.26). Surprisingly, few factors were associated with inaccurate self-reporting in either crude or adjusted analyses; fewer visits to health care providers was significantly associated with overstating compliance.Compliance was markedly overstated in this sample of patients and few characteristics identified those who reported more versus less accurately. Clinicians and researchers who rely on self-reports should be aware of these limits and should take steps to enhance their accuracy.

    View details for DOI 10.1002/pds.819

    View details for Web of Science ID 000188536100002

    View details for PubMedID 14971118

  • Hetastarch and bleeding complications after coronary artery surgery CHEST Avorn, J., Patel, M., Levin, R., Winkelmayer, W. C. 2003; 124 (4): 1437-1442

    Abstract

    Controversy persists concerning the potential association between intraoperative use of hetastarch (ie, hydroxyethyl starch [HES]) and postoperative bleeding in patients undergoing surgery. To determine whether intraoperative HES use is associated with an increased risk of postoperative bleeding following coronary artery bypass graft (CABG) surgery.Case-control study.A large academic medical center in the northeastern United States.A consecutive sample of 238 patients undergoing CABG surgery.Cases consisted of patients who had received either > or = 3 U packed RBCs, > or = 3 U platelets, > or= 3 U fresh frozen plasma, or any cryoprecipitate within 72 h after undergoing a CABG procedure, or who had undergone surgical revision for bleeding. All other CABG surgery patients served as control subjects.In multivariate models that controlled for a wide variety of demographic and clinical characteristics, we found that, compared to patients who did not receive any HES during surgery, those who received 1 U intraoperative HES had more than twice the risk of a bleeding outcome (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.10 to 4.91), and those who received 2 or 3 U HES had more than four times the risk of postoperative bleeding (OR, 4.57; 95% CI, 1.74 to 12.00).HES use in patients undergoing CABG surgery may be associated with a significant risk of postoperative bleeding. A double-blinded, randomized, controlled trial will be necessary to confirm this finding.

    View details for Web of Science ID 000186002500037

    View details for PubMedID 14555577

  • Hydroxyethyl starch and change in renal function in patients undergoing coronary artery bypass graft surgery KIDNEY INTERNATIONAL Winkelmayer, W. C., Glynn, R. J., Levin, R., Avorn, J. 2003; 64 (3): 1046-1049

    Abstract

    Several case reports and clinical lore have suggested that exposure to the colloid hydroxyethyl starch may impair renal function, but few studies have systematically addressed this issue, and several have produced conflicting results. We sought to study the question in a formal analysis of postoperative change in renal function in patients undergoing coronary artery bypass graft (CABG) surgery.We identified 238 consecutive patients who underwent CABG surgery at a large academic medical center. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault formula at baseline as well as on postoperative days 3 and 5. Linear regression analysis was used to study the relation between changes in GFR and intraoperative hydroxyethyl starch administration. Multivariate models controlled for potential demographic, clinical, and surgery-related confounders.Hydroxyethyl starch use was independently associated with a reduction in GFR on both postoperative days 3 and 5, with GFR declining by 7.2 mL/min/1.73 m2 on day 3 per unit of hydroxyethyl starch administered (95% CI, 1.7 to 12.7; P = 0.012), and by 6.6 mL/min/1.73 m2 on day 5 (95% CI, 1.2 to 11.9; P = 0.018).Intraoperative use of hydroxyethyl starch may be associated with modest impairment in renal function in patients undergoing CABG surgery. Randomized clinical trials will be necessary to confirm these findings and to further investigate their clinical implications.

    View details for Web of Science ID 000184732300030

    View details for PubMedID 12911555

  • The cost-effectiveness of maintaining higher hemoglobin targets with erythropoietin in hemodialysis patients KIDNEY INTERNATIONAL Tonelli, M., Winkelmayer, W. C., Jindal, K. K., Owen, W. F., Manns, B. J. 2003; 64 (1): 295-304

    Abstract

    There is uncertainty regarding the appropriate target hemoglobin level in hemodialysis patients treated with erythropoietin (EPO).We sought to determine the incremental cost-effectiveness of prescribing EPO to maintain different target hemoglobin levels, by incorporating the impact of EPO on health-related quality-of-life (HRQOL) issues and adopting the perspective of the health care purchaser. We evaluated the prescription of EPO to maintain target hemoglobin levels of 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, compared with 9.5 to 10.5 g/dL. Model outputs were quality-adjusted life expectancy and costs.The base case analysis estimated intravenous EPO requirements to be 3523, 5078, 6097, and 9341 units three times per week to maintain targets of 9.5 to 10.5, 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, respectively. The cost per quality-adjusted life year (QALY) gained for the 11.0 to 12.0 g/dL target vs. 9.5 to 10.5 g/dL was $55,295 US. For the 12.0 to 12.5 g/dL target compared to 11.0 to 12.0 g/dL, and 14.0 g/dL target compared to 12.0 to 12.5 g/dL, the costs per QALY gained were $613,015 US and $828,215 US, respectively. In sensitivity analysis, clinically implausible reductions in hospitalization or EPO requirements associated with the two higher hemoglobin targets were required to make their incremental cost per QALY gained <$100,000 US.Dosing intravenous EPO to achieve hemoglobin targets of 11.0 to 12.0 g/dL appears to be associated with incremental cost per QALY gained of $50,000 to $60,000, compared with a hemoglobin target of 9.5 to 10.5 g/dL. Aiming for hemoglobin targets in excess of 12.0 g/dL is associated with unfavorable cost-effectiveness ratios and should not be undertaken based on current data.

    View details for Web of Science ID 000183547500035

    View details for PubMedID 12787422

  • Effects of the glutamate carboxypeptidase II (GCP2 1561C > T) and reduced folate carrier (RFC1 80G > A) allelic variants on folate and total homocysteine levels in kidney transplant patients KIDNEY INTERNATIONAL Winkelmayer, W. C., Eberle, C., Sunder-Plassmann, G., Fodinger, M. 2003; 63 (6): 2280-2285

    Abstract

    The effect of the glutamate carboxypeptidase II GCP2 1561C>T and the reduced folate carrier 1 RFC1 80G>A polymorphisms on folate and total homocysteine (tHcy) plasma levels of kidney transplant patients are unknown.In a cross-sectional study of 730 kidney allograft recipients, GCP2 1561C>T, RFC1 80G>A, folate, and tHcy plasma levels were analyzed using linear regression models that allowed dependent covariates to follow a gamma distribution for univariate and multivariate analyses.The allele frequency for GCP2 1561C>T was 0.05, and 0.43 for RFC1 80G>A. Heterozygosity or homozygosity for GCP2 1561C>T was associated with higher folate plasma levels compared to patients without mutation (P < 0.0001), while RFC1 80G>A showed no influence. Multiple testing, also including MTHFR 677C>T and MTHFR 1298A>C, revealed no interaction between the different genotypes and the folate plasma concentration. Neither GCP2 1561C>T nor RFC1 80G>A showed an association with tHcy plasma levels.We conclude that GCP2 1561C>T is associated with elevated folate levels. GCP2 1561C>T and RFC1 80G>A are no major determinants of tHcy plasma levels in kidney transplant patients.

    View details for Web of Science ID 000182781900036

    View details for PubMedID 12753319

  • The nephrologist's role in the management of calcium-phosphorus metabolism in patients with chronic kidney disease KIDNEY INTERNATIONAL Winkelmayer, W. C., Levin, R., Avorn, J. 2003; 63 (5): 1836-1842

    Abstract

    In patients with chronic kidney disease (CKD), timely referral to a nephrologist has been shown to improve outcomes, but the specific care measures mediating these superior outcomes have not been sufficiently described.In a cohort of 3014 patients with CKD, we evaluated whether they had any indicators of calcium-phosphorus metabolism management prior to renal replacement therapy (RRT). These included measurement of parathyroid hormone (PTH) or vitamin D metabolites, or receipt of calcitriol or calcium-containing phosphate binders (CCPB) prior to RRT. Control patients without such care were selected by risk-set matching. We used multivariate conditional logistic regression analysis to test whether use of these interventions was associated with prior nephrologist consultation. We then used Cox proportional hazards models to assess whether implementation of such care was associated with differences in 1-year mortality once RRT was instituted.Only 3.4% of CKD patients had their PTH assessed prior to RRT, and 0.3% had vitamin D status measured. Use of calcitriol (12.2%) and CCPBs (16%) was slightly more prevalent. Seeing a nephrologist was highly associated with use of the tests and drugs studied (odds ratio, 1.28 to 6.46; all P values <0.001), but care by generalists or other specialists was not. Management of calcium-phosphorus metabolism was independently associated with a 35% decreased likelihood of death (hazards ratio=0.65; 95%CI, 0.51 to 0.84) in the first year of RRT.Improvements in management of calcium-phosphorus metabolism in patients with CKD are attributable to nephrologist care and appear to mediate the survival benefit seen in patients who see a nephrologist relatively early in the course of their CKD.

    View details for Web of Science ID 000182041400026

    View details for PubMedID 12675861

  • A propensity analysis of late versus early nephrologist referral and mortality on dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Owen, W. F., Levin, R., Avorn, J. 2003; 14 (2): 486-492

    Abstract

    Previous studies have analyzed the association between late versus early nephrologist referral (LR, ER) and poor clinical outcomes in patients with end-stage renal disease. We sought to determine whether these poor outcomes were causally related to LR, or whether LR was a proxy for poorer access to health care in general. An inception cohort of incident dialysis patients enrolled in the New Jersey Medicare or Medicaid programs was identified. Using a large number of demographic, clinical, and health care utilization covariates, propensity scores (PS) were then calculated to predict whether a given patient had been seen by a nephrologist at 90 d before first dialysis. Cox proportional hazards models were then built to test the association between timing of nephrologist referral and mortality during the first year of dialysis, using PS adjustment and matching to determine whether this association was confounded by other measures of reduced healthcare utilization. Neither adjustment for PS (HR = 1.31; 95% CI, 1.17 to 1.47) nor matching (HR = 1.40; 95% CI, 1.23 to 1.59) materially changed the initial 36% excess mortality in LR compared with ER patients (HR = 1.36; 95% CI, 1.22 to 1.51). Excess mortality among LR was limited to the first 3 mo of dialysis (HR = 1.75; 95% CI, 1.48 to 2.08) but not present thereafter (HR = 1.03; 95% CI, 0.84 to 1.25). Late nephrologist referral is an independent risk factor for early death on dialysis, even after controlling for other indicators of healthcare utilization. Further research is needed to identify patients at particular risk so that interventions to prevent early deaths on dialysis in LR patients can be developed and tested.

    View details for DOI 10.1097/01.ASN.0000046047.66958.C3

    View details for Web of Science ID 000180506500029

    View details for PubMedID 12538751

  • Chronic kidney disease as a risk factor for bleeding complications after coronary artery bypass surgery AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Levin, R., Avorn, J. 2003; 41 (1): 84-89

    Abstract

    The aim of the study is to define the role of chronic kidney disease (CKD) as a risk factor for postoperative bleeding in patients undergoing coronary artery bypass graft (CABG) surgery.This is a retrospective cohort study of 238 consecutive patients who underwent isolated CABG surgery. Patients were followed up for the event of a significant bleed, defined as administration of either three or greater units of packed red blood cells, three or greater units of platelets, three or greater units of fresh frozen plasma, or any cryoprecipitate within 72 hours after a CABG procedure or undergoing a surgical revision for bleeding. Glomerular filtration rate (GFR) at baseline was calculated using the Cockroft-Gault formula. A final multiple logistic regression model was selected from a large set of presurgical and intraoperative covariates by using backward elimination (P > 0.20).After controlling for age, sex, elective versus emergent surgery, intraoperative activated clotting time, serum albumin level, extracorporeal bypass time, and baseline hematocrit, we found that even mild levels of renal impairment were associated with increased risk for postoperative bleeding: patients with a GFR of 40 mL/min or less had six times the odds of postoperative bleeding than patients with a GFR greater than 100 mL/min (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.87 to 22.66); those with a GFR of 41 to 60 mL/min had nearly four times the risk (OR, 3.87; 95% CI, 1.21 to 12.35). Even patients with mild CKD at a GFR of 61 to 80 mL/min were at an elevated risk (OR, 2.11); however, the 95% CI of 0.79 to 5.64 included the null value. Similar results were found when using the cruder Kidney Disease Outcomes Quality Initiative classification of CKD.CKD is associated with risk for postoperative bleeding in patients undergoing CABG surgery, not only at more advanced stages, but probably at relatively mild levels of renal impairment, as well.

    View details for DOI 10.1053/ajkd.2003.50026

    View details for Web of Science ID 000180161100009

    View details for PubMedID 12500224

  • Nephrologist care and mortality in patients with chronic renal insufficiency ARCHIVES OF INTERNAL MEDICINE Avron, J., Bohn, R. L., Levy, E., Levin, R., Owen, W. F., Winkelmayer, W. C., Glynn, R. J. 2002; 162 (17): 2002-2006

    Abstract

    For patients with chronic renal insufficiency, rates of referral to nephrologists are highly variable, and little is known about the effect of such consultation on clinical outcomes. We sought to determine whether early or frequent access to nephrologist care prior to the initiation of dialysis was associated with a difference in mortality rates in the first year after dialysis began.We identified all patients in the New Jersey Medicaid and Medicare programs who began maintenance dialysis during a 6-year period and who had been diagnosed with renal disease more than 12 months prior to dialysis. Use of nephrologist services was documented during this 1-year period, along with other clinical and sociodemographic variables. The outcome measure of our analysis was mortality in the first year after initiation of dialysis.From multivariate analyses, we found that patients who did not see a nephrologist until 90 days or less before initiation of dialysis had a 37% higher likelihood of death in the first year of dialysis compared with patients with earlier referral (95% confidence interval, 1.22-1.52; P<.001). Similarly, those who saw a nephrologist on fewer than 5 occasions in the year prior to dialysis had a 15% higher mortality rate in the first year of dialysis compared with those who had had 5 or more nephrologist visits (95% confidence interval, 1.03-1.28; P =.01).For patients with long-standing renal disease, earlier consultation with a nephrologist and more frequent specialist encounters is associated with lower mortality in the first year of dialysis. These findings need to be confirmed in younger and less indigent patients as well.

    View details for Web of Science ID 000178067100011

    View details for PubMedID 12230424

  • Comparing mortality of elderly patients on hemodialysis versus peritoneal dialysis: A propensity score approach JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Winkelmayer, W. C., Glynn, R. J., Mittleman, M. A., Levin, R., Pliskin, J. S., Avorn, J. 2002; 13 (9): 2353-2362

    Abstract

    The objective of this study was to evaluate differences in mortality over the first year of renal replacement therapy (RRT) between elderly patients starting treatment on hemodialysis (HD) versus peritoneal dialysis (PD). For the period of 1991 to mid-1996, this study defined an inception cohort of all patients aged >65 yr with new-onset chronic RRT who were New Jersey Medicare and/or Medicaid beneficiaries in the year before RRT and who had been diagnosed with renal disease more than 1 yr before RRT. Propensity scores were calculated for first treatment assignment from a large number of baseline covariates. Mortality was then compared among patients initially assigned to HD versus PD using multivariate 90-d interval Cox models controlled for propensity scores and center stratification. Peritoneal dialysis starters had a 16% higher rate of death during the first 90 d of RRT compared with HD patients (hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.96 to 1.42)]. Mortality did not differ between day 91 and 180 (HR, 1.03; 95% CI, 0.71 to 1.51). Thereafter, PD starters again died at a higher rate (HR, 1.45; 95% CI, 1.07 to 1.98). These findings were more pronounced among patients with diabetes. Sensitivity analyses using more stringent criteria to ensure that first treatment choice reflected long-term treatment choice confirmed the presence of an association between PD and mortality. In conclusion, compared with HD, peritoneal dialysis appears to be associated with higher mortality among older patients, particularly among those with diabetes, even after controlling for a large number of risk factors for mortality, propensity scores to control for nonrandom treatment assignment, and center stratification.

    View details for DOI 10.1097/01.ASN.0000025785.41314.76

    View details for Web of Science ID 000177687000018

    View details for PubMedID 12191980

  • Health economic evaluations: The special case of end-stage renal disease treatment MEDICAL DECISION MAKING Winkelmayer, W. C., Weinstein, M. C., Mittleman, M. A., Glynn, R. J., Pliskin, J. S. 2002; 22 (5): 417-430

    Abstract

    This article synthesizes the evidence on the cost-effectiveness of renal replacement therapy and discusses the findings in light of the frequent practice of using the cost-effectiveness of hemodialysis as a benchmark of societal willingness to pay. The authors conducted a meta-analytic review of the medical and economic literature for economic evaluations of hemodialysis, peritoneal dialysis, and kidney transplantation. Cost-effectiveness ratios were translated into 2000 U.S. dollars per life-year (LY) saved. Thirteen studies published between 1968 and 1998 provided such information. The cost effectiveness of center hemodialysis remained within a narrow range of $55,000 to $80,000/LY in most studies despite considerable variation in methodology and imputed costs. The cost-effectiveness of home hemodialysis was found to be between $33,000 and $50,000/LY. Kidney transplantation, however, has become more cost-effective over time, approaching $10,000/LY. Estimates of the cost per life-year gained from hemodialysis have been remarkably stable over the past 3 decades, after adjusting for price levels. Uses of the cost-effectiveness ratio of $55,000/LY for center hemodialysis as a lower boundary of society's willingness to pay for an additional life-year can be supported under certain assumptions.

    View details for DOI 10.1177/027298902236927

    View details for Web of Science ID 000178087500005

    View details for PubMedID 12365484

  • Preventive health care measures before and after start of renal replacement therapy JOURNAL OF GENERAL INTERNAL MEDICINE Winkelmayer, W. C., Owen, W., Glynn, R. J., Levin, R., Avorn, J. 2002; 17 (8): 588-595

    Abstract

    To describe utilization of preventive health care measures in patients with chronic kidney disease (CKD), both in the year prior to onset of renal replacement therapy (RRT), and in the first year of RRT.We identified a large cohort of patients with CKD in the New Jersey Medicaid and Medicare programs with fixed enrollment into the cohort at 1 year prior to RRT. We applied commonly used quality assurance instruments (Health Plan Employer Data and Information Set measures) and defined levels and correlates of use of preventive care measures before and after RRT. These included mammography, Pap smear testing, prostate cancer screening, diabetic eye exams, and glycosylated hemoglobin testing (HbA1c). We employed logistic regression models with adjustment for age, race, gender, comorbidity, timing of first nephrologist contact, socioeconomic status, and calendar year of first RRT.Overall, screening rates were low with the exception of diabetic eye exams. Prostate cancer screening, diabetic eye exams, and HbA1c testing were performed less often after onset of RRT compared to the year before (P < .05). Although screening rates before RRT improved considerably over the period of observation for these measures (P < .05), this was not the case once patients were on RRT.Preventive health care interventions remain underutilized among RRT patients. Greater attention to such preventive measures could lead to significant improvements in the health status of such vulnerable patients. Thus, quality improvement of the general health care for patients on RRT should become a priority in renal health policy.

    View details for Web of Science ID 000177672900002

    View details for PubMedID 12213139

  • Delayed nephrologist referral and inadequate vascular access in patients with advanced chronic kidney failure JOURNAL OF CLINICAL EPIDEMIOLOGY Avorn, J., Winkelmayer, W. C., Bohn, R. L., Levin, R., Glynn, R. J., Levy, E., Owen, W. 2002; 55 (7): 711-716

    Abstract

    We sought to determine whether late referral to a nephrologist in patients with chronic renal failure influences the adequacy of vascular access for hemodialysis. We analyzed data describing all health care encounters for all Medicare and Medicaid patients with end-stage renal failure in New Jersey between January 1991 and June 1996. Patients were required to have been diagnosed with renal disease at least 1 year prior to onset of hemodialysis. In the resulting cohort of 2,398 incident hemodialysis patients, 35% had their first nephrologist consultation < or =90 days prior to initiation of dialysis. After controlling for demographic characteristics, socio-economic status and underlying renal disease, we found that patients who were referred to a nephrologist >90 days prior to onset of hemodialysis were 38% more likely to have undergone predialysis vascular access surgery than those who were referred to a nephrologist < or =90 days before dialysis [OR: 1.38; 95% CI (1.15; 1.64)]. Similarly, patients referred late were 42% more likely to require central venous access for hemodialysis compared to those seen by a nephrologist early [OR: 1.42; 95% CI (1.17; 1.71)]. Inadequate development of vascular access for renal replacement therapy in patients with late nephrologist referral unnecessarily contributes to the burden of disease experienced by this vulnerable patient population.

    View details for Web of Science ID 000176996600011

    View details for PubMedID 12160919

  • Late nephrologist referral and access to renal transplantation TRANSPLANTATION Winkelmayer, W. C., Glynn, R. J., Levin, R., Mittleman, M. A., Pliskin, J. S., Avorn, J. 2002; 73 (12): 1918-1923

    Abstract

    Our aim was to explore a possible association between late nephrologist referral before onset of renal replacement therapy (RRT) and the likelihood of receiving a renal transplant.For the period of 1991 to mid-1996 we defined an inception cohort of all patients with new-onset chronic RRT who were New Jersey Medicare and/or Medicaid beneficiaries in the year before RRT and who had been diagnosed with renal disease more than 1 year before RRT. To control for known risk factors and confounders of access to renal transplantation, we conducted a matched case-control study. Using number of days from onset of RRT to transplantation as the index date for cases, we successfully matched 32 transplant recipients (cases) with 197 controls who shared the cases' age (+/-2 years), gender, race (white/black/other), and year of onset of RRT (+/-1 year) but had not received a transplant on index date. Using conditional logistic regression, we evaluated the effects on the likelihood of transplantation of late referral (< or = 90 days vs. >90 days before first RRT) and socioeconomic status (lower socioeconomic status indicated by enrollment in Medicaid or another state program for the poor), further controlling for comorbidity (Charlson score) in the year before index date.In the full multivariate conditional model, late referral was significantly associated with a much lower rate of renal transplantation (odds ratio [OR]=0.22; 95% confidence interval [CI]: 0.05, 0.97), as were socioeconomic status (OR=0.18; 95% CI: 0.04, 0.82) and comorbidity status (OR=0.69; 95% CI: 0.48, 1.00).Delayed referral of renal patients to a nephrologist before RRT is significantly associated with reduced access to renal transplantation, independent of age, gender, race, socioeconomic and comorbidity status. The validity of our result needs to be confirmed in larger populations.

    View details for Web of Science ID 000176697200012

    View details for PubMedID 12131688

  • Determinants of delayed nephrologist referral in patients with chronic kidney disease AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Glynn, R. J., Levin, R., Owen, W. F., Avorn, J. 2001; 38 (6): 1178-1184

    Abstract

    Late referral to nephrologists of patients with chronic kidney disease (CKD) is a major public health problem because it is prevalent and associated with increased morbidity, mortality, and greater healthcare costs. To identify factors associated with delayed nephrologist referral (first nephrologist visit < 90 days before the onset of renal replacement therapy), we identified a cohort of patients with preexisting CKD that progressed to end-stage renal failure. We developed a logistic regression model to measure the association of specific demographic and clinical covariates with delayed nephrologist referral. Delayed referral was highly associated with older age (P < 0.001), race other than white or black (P = 0.002), and the absence of certain comorbidities: hypertension (P < 0.001), coronary artery disease (P < 0.001), malignancy (P = 0.005), and diabetes (P = 0.02). Associations of late referral with male sex (P = 0.07) and lower socioeconomic status (P = 0.09) were of borderline significance. Patients who were predominantly cared for by a general internist were more likely to be referred late to a nephrologist compared with those cared for by a family or primary care practitioner (P = 0.002) or another subspecialist (P = 0.019). These findings suggest that several factors increase the risk that patients with CKD will have the first nephrologist consultation excessively late in the course of their disease. Although timely access to nephrologist services is important for all patients with advanced CKD, this is of particular concern in older patients, those in certain minority populations, and those in whom the absence of comorbidity may provide a false sense of true risk status.

    View details for DOI 10.1053/ajkd.2001.29207

    View details for Web of Science ID 000172432600004

    View details for PubMedID 11728948

  • Late referral and modality choice in end-stage renal disease KIDNEY INTERNATIONAL Winkelmayer, W. C., Glynn, R. J., Levin, R., Owen, W., Avorn, J. 2001; 60 (4): 1547-1554

    Abstract

    We sought to determine whether late versus early referral to a nephrologist in patients with chronic kidney disease influences the initial choice of hemodialysis (HD) versus peritoneal dialysis (PD) or the likelihood of switching treatment modalities in the first six months of therapy.Using New Jersey Medicare/Medicaid claims, all patients who started RRT between January 1991 and June 1996 and were diagnosed with renal disease more than one year prior to RRT were identified. In the resulting cohort of 3014 patients, 35% had their first nephrologist consultation < or =90 days prior to initiation of dialysis.After controlling for demographic characteristics, socioeconomic status and underlying renal disease, age, black race [Odds ratio (OR) = 0.56], race other than black or white (OR = 0.56), and socioeconomic status (OR = 0.68) influenced the choice of initial treatment modality, but timing of the referral did not. However, patients starting on PD who were referred late were 50% more likely to switch to HD than were patients who saw a nephrologist earlier [Hazard's ratio (HR) = 1.47]. In patients originally on HD, diabetic nephropathy (HR = 1.49) and black race (HR = 0.69) influenced the likelihood of switching to PD, but the timing of referral did not.These results refute earlier findings that late referral may limit access to PD. We found that modality choice depends on factors such as age, race, or socioeconomic status, rather than on than timing of nephrologist referral. Late referral does not influence the likelihood to switch modality in patients starting on HD, but does so in patients starting on PD.

    View details for Web of Science ID 000171127000037

    View details for PubMedID 11576371

  • Optic neuropathy in uremia: An interdisciplinary emergency AMERICAN JOURNAL OF KIDNEY DISEASES Winkelmayer, W. C., Eigner, M., Berger, O., Grisold, W., Leithner, C. 2001; 37 (3)

    Abstract

    Optic neuropathy in uremia is rare. Although the consequences of optic neuropathy-blindness or substantial loss of vision-are devastating, only a few cases have been reported by way of single case reports and case series studies. The reported patients are heterogeneous with regard to the cause of neuropathy. We report the case of a patient with uremic optic neuropathy and summarize the other cases reported in the literature so far. Based on the data available from these reports, we propose a classification system, which includes nonischemic neurotoxic uremic optic neuropathy; ischemic optic neuropathy, more specifically anterior ischemic optic neuropathy; and optic neuropathy as a result of drug side effects, benign intracranial hypertension, and optic neuritis. The immediate institution of dialysis and corticosteroid therapy and correction of anemia and relative hypotension can optimize the chances of visual recovery for these patients. Close collaboration among nephrologists, ophthalmologists, and neurologists is important in this interdisciplinary emergency.

    View details for DOI 10.1053/ajkd.2001.22101

    View details for Web of Science ID 000167495600032

    View details for PubMedID 11228200

  • Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease EXPERT OPINION ON INVESTIGATIONAL DRUGS Sunder-Plassmann, G., Winkelmayer, W. C., Fodinger, M. 2000; 9 (11): 2637-2651

    Abstract

    An elevated total homocysteine (tHcy) plasma concentration is associated with increased morbidity and mortality due to cardiovascular disease in the general population and in patients with impaired renal function. The prevalence of hyperhomocysteinaemia (plasma levels above 15 micromol/l) in the general population is less than 5% and can be as high as 50% in patients with vascular disease. In patients with renal insufficiency, elevated tHcy plasma levels are detected in 50 - 100% of the patients. Total homocysteine plasma levels can be lowered or normalised by folic acid and/or vitamin B(6) and vitamin B(12) supplementation. In patients with advanced chronic renal insufficiency or end-stage renal disease, hyperhomocysteinaemia is partially resistant to folic acid or vitamin therapy. However, higher tHcy plasma levels may also reflect tissue damage and the increase in Hcy after an acute incident such as stroke or myocardial infarction may be necessary for tissue repair mechanisms. This implies, that lowering tHcy may even be harmful to some patients. Currently, prospective studies are underway to clarify whether folate supplementation, with or without additional other vitamins, improves cardiovascular disease morbidity and mortality in the general population, as well as in renal failure patients. While population-wide screening for and treatment of hyperhomocysteinaemia is generally not recommended, treatment of high risk patients may be considered.

    View details for Web of Science ID 000165151300011

    View details for PubMedID 11060826

  • Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: Results of the Vienna multicenter study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Sunder-Plassmann, G., Fodinger, M., Buchmayer, H., Papagiannopoulos, M., Wojcik, J., Kletzmayr, J., Enzenberger, B., Janata, O., Winkelmayer, W. C., Paul, G., Auinger, M., Barnas, U., Horl, W. H. 2000; 11 (6): 1106-1116

    Abstract

    Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.

    View details for Web of Science ID 000087328300014

    View details for PubMedID 10820175

Conference Proceedings


  • Potential Effects of the New Medicare Prospective Payment System on Drug Prescription in End-Stage Renal Disease Care Winkelmayer, W. C. KARGER. 2011: 66-69

    Abstract

    The Centers for Medicaid and Medicare Services have announced a new Prospective Payment System to reimburse the care furnished by dialysis centers to patients with end-stage renal disease (ESRD). As of January 2011, most aspects of the outpatient treatment of patients with ESRD will be included in a single payment. In addition to the items previously included in the Composite Rate, injectable drugs and their oral equivalents will be included in this new capitation payment, as will the laboratory tests required for monitoring maintenance dialysis. As of January 2014, oral-only medications will also be included. Physician payments and payments for inpatient care, as well as for care not directly related to ESRD care will continue to be reimbursed separately. Patterns of medication treatment of ESRD patients will likely be revisited, and one can expect pronounced adjustments. Treatment of anemia will likely shift towards less use of erythropoiesis-stimulating agents and somewhat towards higher use of intravenous iron supplements. Average hemoglobin concentrations will decline. Use of intravenous vitamin D analogues will likely be reduced and substituted with their oral equivalents in many patients. One can also expect a temporary trend towards higher use of calcimetics, since their inclusion in the payment bundle is deferred until 2014. Treatment of problems with vascular access patency and of access infections will likely shift to the inpatient setting, and there may be reluctance to quickly accept recovering patients back to the outpatient setting after vascular access intervention. On aggregate, these changes have the potential to alter patient outcomes, but it is currently unclear how these will be and can be monitored.

    View details for DOI 10.1159/000321856

    View details for Web of Science ID 000287667000011

    View details for PubMedID 21228569

Footer Links:

Stanford Medicine Resources: