Manjula Kurella Tamura

All Publications

• Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs JAMA INTERNAL MEDICINE Tamura, M., Thomas, I., Montez-Rath, M. E., Kapphahn, K., Desai, M., Gale, R. C., Asch, S. M. 2018; 178 (5): 657–64

  Abstract

  The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).Retrospective cohort study of patients from the US Medicare and VA health care systems evaluated 11 215 veterans aged 67 years or older with incident kidney failure between January 1, 2008, and December 31, 2011. Data analysis was performed March 15, 2016, through September 20, 2017.Pre-ESRD nephrology care in Medicare vs VA health care systems.Dialysis treatment and death within 2 years.Of the 11 215 patients included in the study, 11 085 (98.8%) were men; mean (SD) age was 79.1 (6.9) years. Within 2 years of incident kidney failure, 7071 (63.0%) of the patients started dialysis and 5280 (47.1%) died. Patients who received pre-ESRD nephrology care in Medicare were more likely to undergo dialysis compared with patients who received pre-ESRD nephrology care in VA (82% vs 53%; adjusted risk difference, 28 percentage points; 95% CI, 26-30 percentage points). Differences in dialysis initiation between Medicare and VA were more pronounced among patients aged 80 years or older and patients with dementia or metastatic cancer, and less pronounced among patients with paralysis (P < .05 for interaction). Two-year mortality was higher for patients who received pre-ESRD care in Medicare compared with VA (53% vs 44%; adjusted risk difference, 5 percentage points; 95% CI, 3-7 percentage points). The findings were similar in a propensity-matched analysis.Veterans who receive pre-ESRD nephrology care in Medicare receive dialysis more often yet are also more likely to die within 2 years compared with those in VA. The VA's integrated health care system and financing appear to favor lower-intensity treatment for kidney failure in older patients without a concomitant increase in mortality.

  View details for PubMedID 29630695

• Optimizing renal replacement therapy in older adults: a framework for making individualized decisions KIDNEY INTERNATIONAL Tamura, M. K., Tan, J. C., O'Hare, A. M. 2012; 82 (3): 261-269

  Abstract

  It is often difficult to synthesize information about the risks and benefits of recommended management strategies in older patients with end-stage renal disease since they may have more comorbidity and lower life expectancy than patients described in clinical trials or practice guidelines. In this review, we outline a framework for individualizing end-stage renal disease management decisions in older patients. The framework considers three factors: life expectancy, the risks and benefits of competing treatment strategies, and patient preferences. We illustrate the use of this framework by applying it to three key end-stage renal disease decisions in older patients with varying life expectancy: choice of dialysis modality, choice of vascular access for hemodialysis, and referral for kidney transplantation. In several instances, this approach might provide support for treatment decisions that directly contradict available practice guidelines, illustrating circumstances when strict application of guidelines may be inappropriate for certain patients. By combining quantitative estimates of benefits and harms with qualitative assessments of patient preferences, clinicians may be better able to tailor treatment recommendations to individual older patients, thereby improving the overall quality of end-stage renal disease care.

  View details for DOI 10.1038/ki.2011.384

  View details for Web of Science ID 000306370500005

  View details for PubMedID 22089945

  View details for PubMedCentralID PMC3396777

• Regional Variation in Health Care Intensity and Treatment Practices for End-stage Renal Disease in Older Adults JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION O'Hare, A. M., Rodriguez, R. A., Hailpern, S. M., Larson, E. B., Tamura, M. K. 2010; 304 (2): 180-186

  Abstract

  An increasing number of older adults are being treated for end-stage renal disease (ESRD) with long-term dialysis.To determine how ESRD treatment practices for older adults vary across regions with differing end-of-life intensity of care.Retrospective observational study using a national ESRD registry to identify a cohort of 41,420 adults (of white or black race), aged 65 years or older, who started long-term dialysis or received a kidney transplant between June 1, 2005, and May 31, 2006. Regional end-of-life intensity of care was defined using an index from the Dartmouth Atlas of Healthcare.Incidence of treated ESRD (dialysis or transplant), preparedness for ESRD (under the care of a nephrologist, having a fistula [vs graft or catheter] at time of hemodialysis initiation), and end-of-life care practices.Among whites, the incidence of ESRD was progressively higher in regions with greater intensity of care and this trend was most pronounced at older ages. Among blacks, a similar relationship was present only at advanced ages (men aged > or = 80 years and women aged > or = 85 years). Patients living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to be under the care of a nephrologist before the onset of ESRD (62.3% [95% confidence interval {CI}, 61.3%-63.3%] vs 71.1% [95% CI, 69.9%-72.2%], respectively) and less likely to have a fistula (vs graft or catheter) at the time of hemodialysis initiation (11.2% [95% CI, 10.6%-11.8%] vs 16.9% [95% CI, 15.9%-17.8%]). Among patients who died within 2 years of ESRD onset (n = 21,190), those living in regions in the highest compared with lowest quintile of end-of-life intensity of care were less likely to have discontinued dialysis before death (22.2% [95% CI, 21.1%-23.4%] vs 44.3% [95% CI, 42.5%-46.1%], respectively), less likely to have received hospice care (20.7% [95% CI, 19.5%-21.9%] vs 33.5% [95% CI, 31.7%-35.4%]), and more likely to have died in the hospital (67.8% [95% CI, 66.5%-69.1%] vs 50.3% [95% CI, 48.5%-52.1%]). These differences persisted in adjusted analyses.There are pronounced regional differences in treatment practices for ESRD in older adults that are not explained by differences in patient characteristics.

  View details for Web of Science ID 000279811000024

  View details for PubMedID 20628131

  View details for PubMedCentralID PMC3477643

• Functional Status of Elderly Adults before and after Initiation of Dialysis NEW ENGLAND JOURNAL OF MEDICINE Tamura, M. K., Covinsky, K. E., Chertow, G. M., Yaffe, K., Landefeld, C. S., McCulloch, C. E. 2009; 361 (16): 1539-1547

  Abstract

  It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indicating greater functional difficulty).The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp decline in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.

  View details for PubMedID 19828531

• Octogenarians and nonagenarians starting dialysis in the United States ANNALS OF INTERNAL MEDICINE Kurella, M., Covinsky, K. E., Collins, A. J., Chertow, G. M. 2007; 146 (3): 177-183

  Abstract

  The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level.To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis.Observational study.U.S. Renal Data System, a comprehensive, national registry of patients with ESRD.Octogenarians and nonagenarians initiating dialysis between 1996 and 2003.Rates of dialysis initiation and survival.The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions.Survival of patients with incident ESRD who did not begin dialysis could not be assessed.The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly.

  View details for Web of Science ID 000243957400003

  View details for PubMedID 17283348

• Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy KIDNEY INTERNATIONAL REPORTS Bradshaw, C., Gracious, N., Narayanan, R., Narayanan, S., Safeer, M., Nair, G. M., Murlidharan, P., Sundaresan, A., Santhi, S., Prabhakaran, D., Tamura, M., Jha, V., Chertow, G. M., Jeemon, P., Anand, S. 2019; 4 (3): 390–98

  View details for DOI 10.1016/j.ekir.2018.12.007

  View details for Web of Science ID 000460067100007

• Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA SPRINT MIND Investigators for the SPRINT Research Group, Williamson, J. D., Pajewski, N. M., Auchus, A. P., Bryan, R. N., Chelune, G., Cheung, A. K., Cleveland, M. L., Coker, L. H., Crowe, M. G., Cushman, W. C., Cutler, J. A., Davatzikos, C., Desiderio, L., Erus, G., Fine, L. J., Gaussoin, S. A., Harris, D., Hsieh, M., Johnson, K. C., Kimmel, P. L., Tamura, M. K., Launer, L. J., Lerner, A. J., Lewis, C. E., Martindale-Adams, J., Moy, C. S., Nasrallah, I. M., Nichols, L. O., Oparil, S., Ogrocki, P. K., Rahman, M., Rapp, S. R., Reboussin, D. M., Rocco, M. V., Sachs, B. C., Sink, K. M., Still, C. H., Supiano, M. A., Snyder, J. K., Wadley, V. G., Walker, J., Weiner, D. E., Whelton, P. K., Wilson, V. M., Woolard, N., Wright, J. T., Wright, C. B. 2019

  Abstract

  Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.Objective: To evaluate the effect of intensive blood pressure control on risk of dementia.Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018.Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n=4678) or less than 140 mm Hg (standard treatment group; n=4683).Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

  View details for PubMedID 30688979

• Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions. JAMA SPRINT MIND Investigators for the SPRINT Research Group, Nasrallah, I. M., Pajewski, N. M., Auchus, A. P., Chelune, G., Cheung, A. K., Cleveland, M. L., Coker, L. H., Crowe, M. G., Cushman, W. C., Cutler, J. A., Davatzikos, C., Desiderio, L., Doshi, J., Erus, G., Fine, L. J., Gaussoin, S. A., Harris, D., Johnson, K. C., Kimmel, P. L., Kurella Tamura, M., Launer, L. J., Lerner, A. J., Lewis, C. E., Martindale-Adams, J., Moy, C. S., Nichols, L. O., Oparil, S., Ogrocki, P. K., Rahman, M., Rapp, S. R., Reboussin, D. M., Rocco, M. V., Sachs, B. C., Sink, K. M., Still, C. H., Supiano, M. A., Snyder, J. K., Wadley, V. G., Walker, J., Weiner, D. E., Whelton, P. K., Wilson, V. M., Woolard, N., Wright, J. T., Wright, C. B., Williamson, J. D., Bryan, R. N. 2019; 322 (6): 524–34

  Abstract

  Importance: The effect of intensive blood pressure lowering on brain health remains uncertain.Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n=670) and at 4 years of follow-up (n=449); final follow-up date was July 1, 2016.Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n=355) or less than 140 mm Hg (standard treatment, n=315).Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

  View details for DOI 10.1001/jama.2019.10551

  View details for PubMedID 31408137

• Cognitive Impairment in Non-Dialysis-Dependent CKD and the Transition to Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study AMERICAN JOURNAL OF KIDNEY DISEASES Harhay, M. N., Xie, D., Zhang, X., Hsu, C., Vittinghoff, E., Go, A. S., Sozio, S. M., Blumenthal, J., Seliger, S., Chen, J., Deo, R., Dobre, M., Akkina, S., Reese, P. P., Lash, J. P., Yaffe, K., Tamura, M., CRIC Study Investigators 2018; 72 (4): 499–508

  Abstract

  Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease.Retrospective observational study.630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m2, and subsequently initiated maintenance dialysis therapy.Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy.Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant.Multivariable-adjusted logistic regression.Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing.Potential unmeasured confounders; single measure of cognitive function.Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.

  View details for PubMedID 29728316

  View details for PubMedCentralID PMC6153064

• Association Between Hospice Length of Stay, Health Care Utilization, and Medicare Costs at the End of Life Among Patients Who Received Maintenance Hemodialysis JAMA INTERNAL MEDICINE Wachterman, M. W., Hailpern, S. M., Keating, N. L., Tamura, M., O'Hare, A. M. 2018; 178 (6): 792–99

  Abstract

  Patients with end-stage renal disease are less likely to use hospice services than other patients with advanced chronic illness. Little is known about the timing of hospice referral in this population and its association with health care utilization and costs.To examine the association between hospice length of stay and health care utilization and costs at the end of life among Medicare beneficiaries who had received maintenance hemodialysis.This cross-sectional observational study was conducted via the United States Renal Data System registry. Participants were all 770 191 hemodialysis patients in the registry who were enrolled in fee-for-service Medicare and died between January 1, 2000, and December 31, 2014. The dates of analysis were April 2016 to December 2017.Hospital admission, intensive care unit (ICU) admission, and receipt of an intensive procedure during the last month of life; death in the hospital; and costs to the Medicare program in the last week of life.Among 770 191 patients, the mean (SD) age was 74.8 (11.0) years, and 53.7% were male. Twenty percent of cohort members were receiving hospice services when they died. Of these, 41.5% received hospice for 3 days or fewer. In adjusted analyses, compared with patients who did not receive hospice, those enrolled in hospice for 3 days or fewer were less likely to die in the hospital (13.5% vs 55.1%; P < .001) or to undergo an intensive procedure in the last month of life (17.7% vs 31.6%; P < .001) but had higher rates of hospitalization (83.6% vs 74.4%; P < .001) and ICU admission (54.0% vs 51.0%; P < .001) and similar Medicare costs in the last week of life ($10 756 vs $10 871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with progressively lower rates of utilization and costs, especially for those referred more than 15 days before death (35.1% hospitalized and 16.7% admitted to an ICU in the last month of life; the mean Medicare costs in the last week of life were $3221).Overall, 41.5% of hospice enrollees who had been treated with hemodialysis for their end-stage renal disease entered hospice within 3 days of death. Although less likely to die in the hospital and to receive an intensive procedure, these patients were more likely than those not enrolled in hospice to be hospitalized and admitted to the ICU, and they had similar Medicare costs. Without addressing barriers to more timely referral, greater use of hospice may not translate into meaningful changes in patterns of health care utilization, costs, and quality of care at the end of life in this population.

  View details for DOI 10.1001/jamainternmed.2018.0256

  View details for Web of Science ID 000434133500016

  View details for PubMedID 29710217

  View details for PubMedCentralID PMC5988968

• Palliative Care Disincentives in CKD: Changing Policy to Improve CKD Care AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M., O'Hare, A. M., Lin, E., Holdsworth, L. M., Malcolm, E., Moss, A. H. 2018; 71 (6): 866–73

  Abstract

  The dominant health delivery model for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States, which focuses on provision of dialysis, is ill-equipped to address many of the needs of seriously ill patients. Although palliative care may address some of these gaps in care, its integration into advanced CKD care has been suboptimal due to several health system barriers. These barriers include uneven access to specialty palliative care services, underdeveloped models of care for seriously ill patients with advanced CKD, and misaligned policy incentives. This article reviews policies that affect the delivery of palliative care for this population, discusses reforms that could address disincentives to palliative care, identifies quality measurement issues for palliative care for individuals with advanced CKD and ESRD, and considers potential pitfalls in the implementation of new models of integrated palliative care. Reforming health care delivery in ways that remove policy disincentives to palliative care for patients with advanced CKD and ESRD will fill a critical gap in care.

  View details for PubMedID 29510920

  View details for PubMedCentralID PMC5970958

• Hospice Use And End-Of-Life Spending Trajectories In Medicare Beneficiaries On Hemodialysis HEALTH AFFAIRS O'Hare, A. M., Hailpern, S. M., Wachterman, M., Kreuter, W., Katz, R., Hall, Y. N., Montez-Rath, M., Tamura, M., Daratha, K. B. 2018; 37 (6): 980–87

  View details for DOI 10.1377/hlthaff.2017.1181

  View details for Web of Science ID 000463956300020

• Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference KIDNEY INTERNATIONAL Eckardt, K., Bansal, N., Coresh, J., Evans, M., Grams, M. E., Herzog, C. A., James, M. T., Heerspink, H. L., Pollock, C. A., Stevens, P. E., Tamura, M., Tonelli, M. A., Wheeler, D. C., Winkelmayer, W. C., Cheung, M., Hemmelgarn, B. R., Conference Participants 2018; 93 (6): 1281–92

  Abstract

  Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

  View details for PubMedID 29656903

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018

  Abstract

  Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

  View details for PubMedID 29789430

• Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease JAMA INTERNAL MEDICINE Bansal, N., Hailpern, S. M., Katz, R., Hall, Y. N., Tamura, M. K., Kreuter, W., O'Hare, A. M. 2018; 178 (2): 204–9

  Abstract

  Left ventricular assist devices (LVADs) are widely used both as a bridge to heart transplant and as destination therapy in advanced heart failure. Although heart failure is common in patients with end-stage renal disease (ESRD), little is known about outcomes after LVAD implantation in this population.To determine the utilization of and outcomes associated with LVADs in nationally representative cohorts of patients with and without ESRD.We described LVAD utilization and outcomes among Medicare beneficiaries after ESRD onset (defined as having received maintenance dialysis or a kidney transplant) from 2003 to 2013 based on Medicare claims linked to data from the United States Renal Data System (USRDS), a national registry for ESRD. We compared Medicare beneficiaries with ESRD to a 5% sample of Medicare beneficiaries without ESRD.ESRD (vs no ESRD) among patients who underwent LVAD placement.The primary outcome was survival after LVAD placement.Among the patients with ESRD, the mean age was 58.4 (12.1) years and 62.0% (96) were male. Among those without ESRD, the mean age was 62.2 (12.6) years and 75.1% (196) were male. From 2003 to 2013, 155 Medicare beneficiaries with ESRD (median and interquartile range [IQR] days from ESRD onset to LVAD placement were 1655 days [453-3050 days]) and 261 beneficiaries without ESRD in the Medicare 5% sample received an LVAD. During a median follow-up of 762 days (IQR, 92-3850 days), 127 patients (81.9%) with and 95 (36.4%) without ESRD died. more than half of patients with ESRD (80 [51.6%]) compared with 11 (4%) of those without ESRD died during the index hospitalization. The median time to death was 16 days (IQR 2-447 days) for patients with ESRD compared with 2125 days (IQR, 565-3850 days) for those without ESRD. With adjustment for demographics, comorbidity and time period, patients with ESRD had a markedly increased adjusted risk of death (hazard ratio, 36.3; 95% CI, 15.6-84.5), especially in the first 60 days after LVAD placement.Patients with ESRD at the time of LVAD placement had an extremely poor prognosis, with most surviving for less than 3 weeks. This information may be crucial in supporting shared decision-making around treatments for advanced heart failure for patients with ESRD.

  View details for PubMedID 29255896

  View details for PubMedCentralID PMC5801100

• Hospice Use And End-Of-Life Spending Trajectories In Medicare Beneficiaries On Hemodialysis. Health affairs (Project Hope) O'Hare, A. M., Hailpern, S. M., Wachterman, M., Kreuter, W., Katz, R., Hall, Y. N., Montez-Rath, M., Tamura, M. K., Daratha, K. B. 2018; 37 (6): 980–87

  Abstract

  Infrequent and late referral to hospice among patients on dialysis likely reflects the impact of a Medicare payment policy that discourages the concurrent receipt of these services, but it may also reflect these patients' less predictable illness trajectories. Among a national cohort of patients on hemodialysis, we identified four distinct spending trajectories during the last year of life that represented markedly different intensities of care. Within the cohort, 9percent had escalating spending and 13percent had persistently high spending throughout the last year of life, while 41percent had relatively low spending with late escalation, and 37percent had moderate spending with late escalation. Across the four groups, the percentages of patients enrolled in hospice at the time of death were uniformly low ranging from only 19percent of those with persistently high costs to 21percent of those with moderate costs and the median number of days spent in hospice during the last year of life was virtually the same (either five or six days). These findings signal the need for greater flexibility in the provision of end-of-life care in this population.

  View details for PubMedID 29863925

• The Association of Sleep Duration and Quality with CKD Progression JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Ricardo, A. C., Knutson, K., Chen, J., Appel, L. J., Bazzano, L., Carmona-Powell, E., Cohan, J., Tamura, M., Steigerwalt, S., Thornton, J., Weir, M., Turek, N. F., Rahman, M., Van Cauter, E., Lash, J. P., Chronic Renal Insufficiency Cohort 2017; 28 (12): 3708–15

  Abstract

  Evidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5-7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (-1.12 and -0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.

  View details for PubMedID 28912373

  View details for PubMedCentralID PMC5698066

• Hospitalizations and Nursing Facility Stays During the Transition from CKD to ESRD on Dialysis: An Observational Study JOURNAL OF GENERAL INTERNAL MEDICINE Montez-Rath, M. E., Zheng, Y., Tamura, M., Grubbs, V., Winkelmayer, W. C., Chang, T. I. 2017; 32 (11): 1220–27

  Abstract

  There is little information on hospital and nursing facility stays during the transition from pre-dialysis kidney disease to end-stage renal disease treated with dialysis.To examine hospital and nursing facility stays in the years pre- and post-dialysis initiation, and to develop a novel method for visualizing these data.Observational study of patients in the US Renal Data System initiating dialysis from October 2011 to October 2012.Patients aged ≥67 years with Medicare Part A/B coverage for 1 year pre-dialysis initiation.Proportion of patients with ≥1 facility day, and among these, the mean number of days and the mean proportion of time spent in a facility in the first year post-dialysis initiation. We created "heat maps" to represent data visually.Among 28,049 patients, > 60% initiated dialysis in the hospital. Patients with at least 1 facility day spent 37-42 days in a facility in the year pre-dialysis initiation and 59-67 facility days in the year post-dialysis initiation. The duration of facility stay varied by age: patients aged 67-70 years spent 60 (95% CI 57-62) days or 25.8% of the first year post-dialysis initiation in a facility, while patients aged >80 years spent 67 (CI 65-69) days or 36.8% of the first year post-dialysis initiation in a facility. Patterns varied depending on the presence or absence of certain comorbid conditions, with dementia having a particularly large effect: patients with dementia spent approximately 50% of the first year post-dialysis initiation in a facility, regardless of age.Older patients, particularly octogenarians and patients with dementia or other comorbidities, spend a large proportion of time in a facility during the first year after dialysis initiation. Our heat maps provide a novel and concise visual representation of a large amount of quantitative data regarding expected outcomes after initiation of dialysis.

  View details for PubMedID 28808869

  View details for PubMedCentralID PMC5653560

• Measures of Kidney Disease and the Risk of Venous Thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study AMERICAN JOURNAL OF KIDNEY DISEASES Cheung, K. L., Zakai, N. A., Folsom, A. R., Tamura, M., Peralta, C. A., Judd, S. E., Callas, P. W., Cushman, M. 2017; 70 (2): 182–90

  Abstract

  Kidney disease has been associated with venous thromboembolism (VTE) risk, but results conflict and there is little information regarding blacks.Prospective cohort study.30,239 black and white adults 45 years or older enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 2003 to 2007.Estimated glomerular filtration rate (eGFR) using the combined creatinine-cystatin C (eGFRcr-cys) equation and urinary albumin-creatinine ratio (ACR).The primary outcome was adjudicated VTE, and secondary outcomes were provoked and unprovoked VTE, separately. Mortality was a competing-risk event.During 4.6 years of follow-up, 239 incident VTE events occurred over 124,624 person-years. Cause-specific HRs of VTE were calculated using proportional hazards regression adjusted for age, sex, race, region of residence, and body mass index. Adjusted VTE HRs for eGFRcr-cys of 60 to <90, 45 to <60, and <45 versus ≥90mL/min/1.73m2 were 1.28 (95% CI, 0.94-1.76), 1.30 (95% CI, 0.77-2.18), and 2.13 (95% CI, 1.21-3.76). Adjusted VTE HRs for ACR of 10 to <30, 30 to <300, and ≥300 versus <10mg/g were 1.14 (95% CI, 0.84-1.56), 1.15 (95% CI, 0.79-1.69), and 0.64 (95% CI, 0.25-1.62). Associations were similar for provoked and unprovoked VTE.Single measurement of eGFR and ACR may have led to misclassification. Smaller numbers of events may have limited power.There was an independent association of low eGFR (<45 vs ≥90mL/min/1.73m2) with VTE risk, but no association of ACR and VTE.

  View details for DOI 10.1053/j.ajkd.2016.10.039

  View details for Web of Science ID 000406047500011

  View details for PubMedID 28126238

  View details for PubMedCentralID PMC5522772

• Research Priorities for Palliative Care for Older Adults with Advanced Chronic Kidney Disease JOURNAL OF PALLIATIVE MEDICINE O'Hare, A. M., Song, M., Tamura, M. K., Moss, A. H. 2017; 20 (5): 453-460

  Abstract

  Older adults with advanced chronic kidney disease (CKD) often have multiple comorbid conditions, a high symptom burden, and limited life expectancy. There is mounting concern that the intensive patterns of care that many of these patients receive at the end of life are discordant with their values and preferences. The nephrology community has recognized that there are significant unmet palliative care needs in this population. In this article, we identify three broad areas of knowledge deficit where more evidence is needed to support the "best care possible" for this population: (1) what matters most to older adults with advanced CKD and their caregivers near the end of life; (2) how the nephrology community can best support older adults with advanced CKD to navigate complex treatment decisions throughout their illness; and (3) how the healthcare system should be reconfigured to promote patient- and family-centered care for older adults with advanced CKD. Research priorities include identifying opportunities for improving the end-of-life experience of older adults with CKD and their caregivers; developing and testing communication interventions before and during dialysis to ensure that treatment decisions reflect patients' preferences; and assessing the effectiveness of palliative care in improving quality of life for patients and caregivers, satisfaction with care, and aligning treatment decisions with patient goals and preferences.

  View details for DOI 10.1089/jpm.2016.0571

  View details for Web of Science ID 000400572600006

  View details for PubMedID 28463635

• Loss of executive function after dialysis initiation in adults with chronic kidney disease KIDNEY INTERNATIONAL Tamura, M. K., Vittinghoff, E., Hsu, C., Tam, K., Seliger, S. L., Sozio, S., Fischer, M., Chen, J., Lustigova, E., Strauss, L., Deo, R., Go, A. S., Yaffe, K. 2017; 91 (4): 948-953

  View details for Web of Science ID 000397835900023

• Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Montez-Rath, M. E., Hall, Y. N., Katz, R., O'Hare, A. M. 2017; 12 (3): 435-442

  Abstract

  Little is known about the relation between the content of advance directives and downstream treatment decisions among patients receiving maintenance dialysis. In this study, we determined the prevalence of advance directives specifying treatment limitations and/or surrogate decision-makers in the last year of life and their association with end-of-life care among nursing home residents.Using national data from 2006 to 2007, we compared the content of advance directives among 30,716 nursing home residents receiving dialysis to 30,825 nursing home residents with other serious illnesses during the year before death. Among patients receiving dialysis, we linked the content of advance directives to Medicare claims to ascertain site of death and treatment intensity in the last month of life.In the last year of life, 36% of nursing home residents receiving dialysis had a treatment-limiting directive, 22% had a surrogate decision-maker, and 13% had both in adjusted analyses. These estimates were 13%-27%, 5%-11%, and 6%-13% lower, respectively, than for decedents with other serious illnesses. For patients receiving dialysis who had both a treatment-limiting directive and surrogate decision-maker, the adjusted frequency of hospitalization, intensive care unit admission, intensive procedures, and inpatient death were lower by 13%, 17%, 13%, and 14%, respectively, and hospice use and dialysis discontinuation were 5% and 7% higher compared with patients receiving dialysis lacking both components.Among nursing home residents receiving dialysis, treatment-limiting directives and surrogates were associated with fewer intensive interventions and inpatient deaths, but were in place much less often than for nursing home residents with other serious illnesses.

  View details for DOI 10.2215/CJN.07510716

  View details for Web of Science ID 000396822000011

  View details for PubMedCentralID PMC5338713

• Optimizing the Transition to End-Stage Renal Disease SEMINARS IN NEPHROLOGY Tamura, M. 2017; 37 (2): 113

  View details for DOI 10.1016/j.semnephrol.2016.12.010

  View details for Web of Science ID 000399852900001

  View details for PubMedID 28410644

• Effect of a Dialysis Access Coordinator on Preemptive Access Placement among Veterans: A Quality Improvement Initiative AMERICAN JOURNAL OF NEPHROLOGY Gale, R. C., Kehoe, D., Lit, Y. Z., Asch, S. M., Tamura, M. K. 2017; 45 (1): 14-21

  Abstract

  Preemptive placement of permanent dialysis access is recommended in order to reduce the morbidity associated with central venous catheters. We assessed the effect of a dialysis access coordinator on preemptive access placement in veterans who are at high risk for end-stage renal disease (ESRD).Pre-post evaluation of a dialysis access coordinator in the nephrology clinics of the Veterans Affairs Palo Alto. The access coordinator streamlined access referrals, prioritized surgical waiting lists and addressed patient barriers. We compared the frequency of preemptive access referral, surgery, and use for dialysis during the intervention period, July 1, 2013 to May 31, 2016, to a pre-intervention period, January 1, 2011 to December 31, 2013, among all patients with a predicted 1-year risk for ESRD ≥20%.There were 156 patients in the historical cohort and 131 in the intervention cohort. The mean age was 69.9 ± 11.6 years and the mean estimated glomerular filtration rate was 14.5 ± 5.7 ml/min/1.73 m2. The intervention was associated with an 11.8% increase in access referral (p value = 0.03), and a 9.4% increase in completed access surgery (p value = 0.05). Increases in permanent access at the start of dialysis (15.2%), and functional permanent access at the start of dialysis (12.4%) did not reach statistical significance. Among patients who received access surgery, there was no significant difference in the prevalence of unused access.Implementation of an access coordinator was associated with a modest increase in preemptive access placement among patients who are at high risk for ESRD without increasing the prevalence of unused access.

  View details for DOI 10.1159/000452346

  View details for Web of Science ID 000391428900003

• Trends in Receipt of Intensive Procedures at the End of Life Among Patients Treated With Maintenance Dialysis AMERICAN JOURNAL OF KIDNEY DISEASES Eneanya, N. D., Hailpern, S. M., O'Hare, A. M., Tamura, M. K., Katz, R., Kreuter, W., Montez-Rath, M. E., Hebert, P. L., Hall, Y. N. 2017; 69 (1): 60-68

  Abstract

  Many dialysis patients receive intensive procedures intended to prolong life at the very end of life. However, little is known about trends over time in the use of these procedures. We describe temporal trends in receipt of inpatient intensive procedures during the last 6 months of life among patients treated with maintenance dialysis.Mortality follow-back study.649,607 adult Medicare beneficiaries on maintenance dialysis therapy who died in 2000 to 2012.Period of death (2000-2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74, 75-79, 80-84, and ≥85 years), and race/ethnicity (Hispanic, non-Hispanic black, or non-Hispanic white).Receipt of an inpatient intensive procedure (defined as invasive mechanical ventilation/intubation, tracheostomy, gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or cardiopulmonary resuscitation) during the last 6 months of life.Overall, 34% of cohort patients received an intensive procedure in the last 6 months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and 1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of intensive procedures increased more markedly over time in younger versus older patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15-1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive procedures increased more dramatically for Hispanic patients than for non-Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14-1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively).Data sources do not provide insight into reasons for observed trends in the use of intensive procedures.Among patients treated with maintenance dialysis, there is a trend toward more frequent use of intensive procedures at the end of life, especially in younger patients and those of Hispanic ethnicity.

  View details for DOI 10.1053/j.ajkd.2016.07.028

  View details for Web of Science ID 000390526300014

  View details for PubMedCentralID PMC5182121

• Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Chertow, G. M., Depner, T. A., Nissenson, A. R., Schiller, B., Mehta, R. L., Liu, S., Sirich, T. L. 2016; 27 (12): 3780-3787

  Abstract

  Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.

  View details for DOI 10.1681/ASN.2016010039

  View details for PubMedID 27444566

• Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge? Journal of cerebral blood flow and metabolism Jahanian, H., Christen, T., Moseley, M. E., Pajewski, N. M., Wright, C. B., Tamura, M. K., Zaharchuk, G. 2016

  Abstract

  Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2 )= 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  View details for PubMedID 27683452

• Cognitive Impairment and Progression of CKD AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Yaffe, K., Hsu, C., Yang, J., Sozio, S., Fischer, M., Chen, J., Ojo, A., DeLuca, J., Xie, D., Vittinghoff, E., Go, A. S. 2016; 68 (1): 77-83

  View details for DOI 10.1053/j.ajkd.2016.01.026

  View details for Web of Science ID 000378636100016

• A survey of views and practice patterns of dialysis medical directors toward end-of-life decision making for patients with end-stage renal disease. Palliative medicine Fung, E., Slesnick, N., Kurella Tamura, M., Schiller, B. 2016; 30 (7): 653-660

  Abstract

  Patients with end-stage renal disease report infrequent end-of-life discussions, and nephrology trainees report feeling unprepared for end-of-life decision making, but the views of dialysis medical directors have not been studied.Our objective is to understand dialysis medical directors' views and practice patterns on end-of-life decision making for patients with ESRD.We administered questionnaires to dialysis medical directors during medical director meetings of three different dialysis organizations in 2013. Survey questions corresponded to recommendations from the Renal Physicians Association clinical practice guidelines on initiation and withdrawal of dialysis.There were 121 medical director respondents from 28 states.The majority of respondents felt "very prepared" (66%) or "somewhat prepared" (29%) to participate in end-of-life decisions and most (80%) endorsed a model of shared decision making. If asked to do so, 70% of the respondents provided prognostic information "often" or "nearly always." For patients with a poor prognosis, 36% of respondents would offer a time-limited trial of dialysis "often" or "nearly always", while 56% of respondents would suggest withdrawal from dialysis "often" or "nearly always" for those with a poor prognosis currently receiving dialysis therapy. Patient resistance and fear of taking away hope were the most commonly cited barriers to end-of-life discussions.Views and reported practice patterns of medical directors are consistent with clinical practice guidelines for end-of-life decision making for patients with end-stage renal disease but inconsistent with patient perceptions.

  View details for DOI 10.1177/0269216315625856

  View details for PubMedID 26814215

• Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults NEUROLOGY Tamura, M. K., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

  Abstract

  To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

  View details for DOI 10.1212/WNL.0000000000002527

  View details for Web of Science ID 000372853000007

  View details for PubMedCentralID PMC4818564

• Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults. Neurology Kurella Tamura, M., Pajewski, N. M., Bryan, R. N., Weiner, D. E., Diamond, M., Van Buren, P., Taylor, A., Beddhu, S., Rosendorff, C., Jahanian, H., Zaharchuk, G. 2016; 86 (13): 1208-1216

  Abstract

  To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults.We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics.There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g).Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV.

  View details for DOI 10.1212/WNL.0000000000002527

  View details for PubMedID 26920359

• Anemia and risk for cognitive decline in chronic kidney disease BMC NEPHROLOGY Tamura, M. K., Vittinghoff, E., Yang, J., Go, A. S., Seliger, S. L., Kusek, J. W., Lash, J., Cohen, D. L., Simon, J., Batuman, V., Ordonez, J., Makos, G., Yaffe, K. 2016; 17

  View details for DOI 10.1186/s12882-016-0226-6

  View details for Web of Science ID 000369153500001

• Epidemiology and Public Health Concerns of CKD in Older Adults ADVANCES IN CHRONIC KIDNEY DISEASE Fung, E., Tamura, M. K. 2016; 23 (1): 8-11

  View details for DOI 10.1053/j.ackd.2015.10.001

  View details for Web of Science ID 000368652200003

• Prevalence and correlates of functional dependence among maintenance dialysis patients HEMODIALYSIS INTERNATIONAL Kavanagh, N. T., Schiller, B., Saxena, A. B., Thomas, I., Tamura, M. K. 2015; 19 (4): 593-600

  View details for DOI 10.1111/hdi.12286

  View details for Web of Science ID 000362584500030

• Menopausal symptoms in women with chronic kidney disease. Menopause (New York, N.Y.) Cheung, K. L., Stefanick, M. L., Allison, M. A., LeBlanc, E. S., Vitolins, M. Z., Shara, N., Chertow, G. M., Winkelmayer, W. C., Kurella Tamura, M. 2015; 22 (9): 1006-1011

  Abstract

  This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

  View details for DOI 10.1097/GME.0000000000000416

  View details for PubMedID 25628057

• Introduction: Sleep and Neurologic Disorders in Chronic Kidney Disease. Seminars in nephrology Unruh, M., Tamura, M. K. 2015; 35 (4): 303

  View details for PubMedID 26355248

• Nondisease-Specific Problems and All-Cause Mortality among Older Adults with CKD: The REGARDS Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Bowling, C. B., Booth, J. N., Gutierrez, O. M., Tamura, M. K., Huang, L., Kilgore, M., Judd, S., Warnock, D. G., McClellan, W. M., Allman, R. M., Muntner, P. 2014; 9 (10): 1737-1745

  Abstract

  The term "nondisease-specific" has been used to describe problems that cross multiple domains of health and are not necessarily the result of a single underlying disease. Although individuals with reduced eGFR and elevated albumin-to-creatinine ratio have many comorbidities, the prevalence of and outcomes associated with nondisease-specific problems have not been well studied.Participants included 3557 black and white United States adults ≥75 years of age from the Reasons for Geographic and Racial Differences in Stroke Study. Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Hazard ratios for mortality over a median (interquartile range) of 5.4 (4.2-6.9) years of follow-up associated with one, two, or three to six nondisease-specific problems were calculated and stratified by eGFR (≥60, 45-59, and <45 ml/min per 1.73 m(2)) and separately, albumin-to-creatinine ratio (<30, 30-299, and ≥300 mg/g). Secondary outcomes included hospitalizations and emergency department visits over 1.8 (0.7-4.0) and 2.3 (0.9-4.7) years of follow-up, respectively.The prevalence of nondisease-specific problems was more common at lower eGFR and higher albumin-to-creatinine ratio levels. Within each eGFR and albumin-to-creatinine ratio strata, the risk for mortality was higher among those with a greater number of nondisease-specific problems. For example, among those with an eGFR=45-59 ml/min per 1.73 m(2), the multivariable adjusted hazard ratios (95% confidence intervals) for mortality associated with one, two, or three to six nondisease-specific problems were 1.17 (0.78 to 1.76), 1.95 (1.24 to 3.07), and 2.44 (1.39 to 4.27; P trend <0.001). Risk for hospitalization and emergency department visits was higher among those with more nondisease-specific problems within eGFR and albumin-to-creatinine ratio strata.Among older adults, nondisease-specific problems commonly co-occur with reduced eGFR and elevated albumin-to-creatinine ratio. Identification of nondisease-specific problems may provide mortality risk information independent of measures of kidney function.

  View details for DOI 10.2215/CJN.00880114

  View details for Web of Science ID 000342713100011

  View details for PubMedID 25278551

• Performance of the NINDS-CSN 5-Minute Protocol in a National Population-Based Sample JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Kennedy, R. E., Wadley, V. G., McClure, L. A., Letter, A. J., Unverzagt, F. W., Crowe, M., Nyenhius, D., Kelley, B. J., Kana, B., Marceaux, J., Tamura, M. K., Howard, V., Howard, G. 2014; 20 (8): 856-867

  Abstract

  In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI.

  View details for DOI 10.1017/S1355617714000733

  View details for Web of Science ID 000344951500009

  View details for PubMedCentralID PMC4452126

• Prognostic stratification in older adults commencing dialysis. 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; 69 (8): 1033-1039

  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

• Thematic Synthesis of Qualitative Studies on Patient and Caregiver Perspectives on End-of-Life Care in CKD AMERICAN JOURNAL OF KIDNEY DISEASES Tong, A., Cheung, K. L., Nair, S. S., Tamura, M. K., Craig, J. C., Winkelmayer, W. C. 2014; 63 (6): 913-927

  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 Web of Science ID 000336385900009

  View details for PubMedID 24411716

• Effects of Frequent Hemodialysis on Perceived Caregiver Burden in the Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Suri, R. S., Larive, B., Hall, Y., Kimmel, P. L., Kliger, A. S., Levin, N., Tamura, M. K., Chertow, G. M. 2014; 9 (5): 936-942

  Abstract

  Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers.In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared.In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02).Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

  View details for DOI 10.2215/CJN.07170713

  View details for Web of Science ID 000335519300017

  View details for PubMedID 24721892

• Does chronic kidney disease affect outcomes after major abdominal surgery? Results from the national surgical quality improvement program. Journal of gastrointestinal surgery Cloyd, J. M., Ma, Y., Morton, J. M., Kurella Tamura, M., Poultsides, G. A., Visser, B. C. 2014; 18 (3): 605-612

  Abstract

  The impact of chronic kidney disease (CKD) and end-stage renal disease on outcomes following major abdominal surgery is not well defined.The 2008 NSQIP database was queried to identify adult patients undergoing complex abdominal surgery (major colorectal, hepatobiliary, pancreatic, gastric, and esophageal operations). Thirty-day morbidity and mortality in patients on hemodialysis (HD) versus patients not on HD were compared. The impact of preoperative renal insufficiency, measured by glomerular filtration rate (GFR), on morbidity and mortality was then assessed in non-dialysis patients.Of 24,572 patients who underwent major abdominal operations, excluding emergency cases, only 149 (0.6 %) were on HD preoperatively. Thirty-day mortality in the HD group was 12.8 % compared to 1.8 % for those not on HD (p < 0.0001). Overall complication rate was 23.5 versus 12.3 % (p < 0.0001). In particular, rates of pneumonia (6.7 vs 3.0 %, p < 0.05) and sepsis (12.8 vs 5.3 %, p < 0.001) were higher in patients on HD. In patients not on HD, GFR was significantly predictive of postoperative mortality after controlling for age, gender, race, emergency status, and comorbidities. Compared to patients with normal preoperative kidney function (GFR, 75-90 ml/min/1.73 m(2)), even modest CKD (GFR, 45-60 ml/min/1.73 m(2)) was associated with increased postoperative mortality (odds ratio (OR), 1.62). With greater impairment in kidney function, postoperative mortality was even more marked (GFR, 30-45 ml/min/1.73 m(2) and OR, 2.84; GFR, 15-30 ml/min/1.73 m(2) and OR, 5.56). In addition, CKD was independently associated with increased postoperative complications.Any degree of preoperative kidney impairment, even mild asymptomatic disease, is associated with clinically significant increases in 30-day postoperative morbidity and mortality following major abdominal surgery.

  View details for DOI 10.1007/s11605-013-2390-3

  View details for PubMedID 24241964

• Aging and Chronic Kidney Disease: The Impact on Physical Function and Cognition JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Anand, S., Johansen, K. L., Tamura, M. K. 2014; 69 (3): 315-322

  Abstract

  Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

  View details for DOI 10.1093/gerona/glt109

  View details for Web of Science ID 000333384800011

• Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information End-Stage Renal Disease Prevention in Older Adults JAMA INTERNAL MEDICINE O'Hare, A. M., Hotchkiss, J. R., Tamura, M. K., Larson, E. B., Hemmelgarn, B. R., Batten, A., Covinsky, K. E. 2014; 174 (3): 391-397

  Abstract

  Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.Level of estimated glomerular filtration rate (eGFR) and proteinuria.Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.

  View details for DOI 10.1001/jamainternmed.2013.13328

  View details for Web of Science ID 000333052100019

  View details for PubMedID 24424348

  View details for PubMedCentralID PMC4119007

• Educational programs improve the preparation for dialysis and survival of patients with chronic kidney disease KIDNEY INTERNATIONAL Tamura, M. K., Li, S., Chen, S., Cavanaugh, K. L., Whaley-Connell, A. T., McCullough, P. A., Mehrotra, R. L. 2014; 85 (3): 686-692

  Abstract

  Preparation for end-stage renal disease (ESRD) is widely acknowledged to be suboptimal in the United States. We sought to determine whether participation in a kidney disease screening and education program resulted in improved ESRD preparation and survival in 595 adults who developed ESRD after participating in the National Kidney Foundation Kidney Early Evaluation Program (KEEP), a community-based screening and education program. Non-KEEP patients were selected from a national ESRD registry and matched to KEEP participants based on demographic and clinical characteristics. The main outcomes were pre-ESRD nephrologist care, placement of permanent vascular access, use of peritoneal dialysis, pre-emptive transplant wait listing, transplantation, and mortality after ESRD. Participation in KEEP was associated with significantly higher rates of pre-ESRD nephrologist care (76.0% vs. 69.3%), peritoneal dialysis (10.3% vs. 6.4%), pre-emptive transplant wait listing (24.2% vs. 17.1%), and transplantation (9.7% vs. 6.4%) but not with higher rates of permanent vascular access (23.4% vs. 20.1%). Participation in KEEP was associated with a lower risk for mortality (hazard ratio 0.80), but this was not statistically significant after adjusting for ESRD preparation. Thus, participation in a voluntary community kidney disease screening and education program was associated with higher rates of ESRD preparation and survival.

  View details for DOI 10.1038/ki.2013.369

  View details for Web of Science ID 000332225600028

  View details for PubMedID 24067435

• Aging and chronic kidney disease: the impact on physical function and cognition. journals of gerontology. Series A, Biological sciences and medical sciences Anand, S., Johansen, K. L., Kurella Tamura, M. 2014; 69 (3): 315-322

  Abstract

  Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

  View details for DOI 10.1093/gerona/glt109

  View details for PubMedID 23913934

• Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

  View details for DOI 10.1371/journal.pone.0092539

  View details for PubMedID 24651703

• Vitamin d deficiency and mortality in patients receiving dialysis: the comprehensive dialysis study. Journal of renal nutrition Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Kurella Tamura, M. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for PubMedID 23876600

• Vitamin D Deficiency and Mortality in Patients Receiving Dialysis: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Kaysen, G. A., Tamura, M. K. 2013; 23 (6): 422-427

  Abstract

  Although several studies have shown poorer survival among individuals with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested the hypothesis that patients new to dialysis with low serum concentrations of 25-OH vitamin D would experience higher mortality and hospitalizations.The CDS is a prospective cohort study.We recruited participants from 56 dialysis units located throughout the United States.We obtained data on demographics, comorbidites, and laboratory values from the CDS Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728). Participants provided baseline serum samples for 25-OH vitamin D measurements.We ascertained time to death and first hospitalization as well as number of first-year hospitalizations via the U.S. Renal Data System standard analysis files. We used Cox proportional hazards to determine the association between 25-OH vitamin D tertiles and survival and hospitalization. For number of hospitalizations in the first year, we used negative binomial regression.The analytic cohort was composed of 256 patients with Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of participants was 62 (±14.0) years, and mean follow-up was 3.8 years. Patients with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95% confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL) experienced a higher rate of hospitalizations in the first year (incidence rate ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for lowest tertile).We found a sizeable increase in mortality and hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

  View details for DOI 10.1053/j.jrn.2013.05.003

  View details for Web of Science ID 000327007600007

• Frailty and Dialysis Initiation SEMINARS IN DIALYSIS Johansen, K. L., Delgado, C., Bao, Y., Tamura, M. K. 2013; 26 (6): 690-696

  Abstract

  Frailty is a physiologic state of increased vulnerability to stressors that results from decreased physiologic reserves or dysregulation of multiple physiologic systems. The construct of frailty has been operationalized as a composite of poor physical function, exhaustion, low physical activity, and weight loss. Several studies have now examined the prevalence of frailty among chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients and have found frailty to be more common among individuals with CKD than among those without. Furthermore, frailty is associated with adverse outcomes among incident dialysis patients, including higher risk of hospitalization and death. Recent evidence shows that frail patients are started on dialysis earlier (at a higher estimated glomerular filtration rate [eGFR]) on average than nonfrail patients, but it remains unclear whether these patients' frailty is a result of uremia or is independent of CKD. The survival disadvantage that has been associated with early initiation of dialysis in observational studies could be mediated in part through confounding on the basis of unmeasured frailty. However, available data do not suggest improvement in frailty upon initiation of dialysis; rather, the trajectory appears to be toward higher levels of dependence in activities of daily living (ADLs) after dialysis initiation. Overall, there are no data to suggest that frail patients derive any benefit from early initiation of dialysis either in the form of improved survival or functional status.

  View details for DOI 10.1111/sdi.12126

  View details for Web of Science ID 000327030200010

  View details for PubMedID 24004376

• Pre-ESRD Changes in Body Weight and Survival in Nursing Home Residents Starting Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Stack, S., Chertow, G. M., Johansen, K. L., Si, Y., Tamura, M. K. 2013; 8 (10): 1734-1740

  Abstract

  Among patients receiving maintenance dialysis, weight loss at any body mass index is associated with mortality. However, it is not known whether weight changes before dialysis initiation are associated with mortality and if so, what risks are associated with weight gain or loss.Linking data from the US Renal Data System to a national registry of nursing home residents, this study identified 11,090 patients who started dialysis between January of 2000 and December of 2006. Patients were categorized according to weight measured between 3 and 6 months before dialysis initiation and the percentage change in body weight before dialysis initiation (divided into quintiles). The outcome was mortality within 1 year of starting dialysis.There were 361 patients (3.3%) who were underweight (Quételet's [body mass] index<18.5 kg/m(2)) and 4046 patients (36.5%) who were obese (body mass index ≥ 30 kg/m(2)) before dialysis initiation. The median percentage change in body weight before dialysis initiation was -6% (interquartile range=-13% to 1%). There were 6063 deaths (54.7%) over 1 year of follow-up. Compared with patients with minimal weight changes (-3% to 3%, quintile 4), patients with weight loss ≥ 15% (quintile 1) had 35% higher risk for mortality (95% confidence interval, 1.25 to 1.47), whereas those patients with weight gain ≥ 4% (quintile 5) had a 24% higher risk for mortality (95% confidence interval, 1.14 to 1.35) adjusted for baseline body mass index and other confounders.Among nursing home residents, changes in body weight in advance of dialysis initiation are associated with significantly higher 1-year mortality.

  View details for DOI 10.2215/CJN.01410213

  View details for PubMedID 24009221

• Five Policies to Promote Palliative Care for Patients with ESRD CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Meier, D. E. 2013; 8 (10): 1783-1790

  Abstract

  Patients with ESRD experience complex and costly care that does not always meet their needs. Palliative care, which focuses on improving quality of life and relieving suffering for patients with serious illnesses, could address a large unmet need among patients with ESRD. Strengthening palliative care is a top policy priority for health reform efforts based on strong evidence that palliative care improves value. This commentary outlines palliative care policies for patients with ESRD and is directed at policymakers, dialysis providers, nephrology professional societies, accreditation organizations, and funding agencies who play a key role in the delivery and determination of quality of ESRD care. Herein we suggest policies to promote palliative care for patients with ESRD by addressing key barriers, including the lack of access to palliative care, lack of capacity to deliver palliative care, and a limited evidence base. We also provide examples of how these policies could be implemented within the existing ESRD care infrastructure.

  View details for DOI 10.2215/CJN.02180213

  View details for Web of Science ID 000325268200021

  View details for PubMedID 23744000

• Impact of frequent hemodialysis on anemia management: results from the Frequent Hemodialysis Network (FHN) Trials NEPHROLOGY DIALYSIS TRANSPLANTATION Ornt, D. B., Larive, B., Rastogi, A., Rashid, M., Daugirdas, J. T., Hernandez, A., Tamura, M. K., Suri, R. S., Levin, N. W., Kliger, A. S. 2013; 28 (7): 1888-1898

  View details for DOI 10.1093/ndt/gfs593

  View details for Web of Science ID 000321821900034

• Risk Factors for ESRD in Individuals With Preserved Estimated GFR With and Without Albuminuria: Results From the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Chang, T. I., Li, S., Chen, S., Peralta, C. A., Shlipak, M. G., Fried, L. F., Whaley-Connell, A. T., McCullough, P. A., Tamura, M. K. 2013; 61 (4): S4-S11

  Abstract

  Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD.This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ≥ 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death.During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure.In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.

  View details for DOI 10.1053/j.ajkd.2012.12.016

  View details for PubMedID 23507268

• Effect of More Frequent Hemodialysis on Cognitive Function in the Frequent Hemodialysis Network Trials AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Unruh, M. L., Nissenson, A. R., Larive, B., Eggers, P. W., Gassman, J., Mehta, R. L., Kliger, A. S., Stokes, J. B. 2013; 61 (2): 228-237

  Abstract

  Cognitive impairment is common in patients with end-stage renal disease receiving hemodialysis 3 times per week.Randomized clinical trial.218 individuals participating in the Frequent Hemodialysis Network (FHN) Daily Trial and 81 participating in the FHN Nocturnal Trial.The Daily Trial tested in-center hemodialysis 6 times per week versus 3 times per week. The Nocturnal Trial tested home nocturnal hemodialysis 6 times per week versus home or in-center hemodialysis 3 times per week.Cognitive function was measured at baseline, month 4, and month 12. The primary outcome was performance on the Trail-Making Test, Form B, a measure of executive function, and a secondary outcome was performance on the Modified Mini-Mental State Examination, a measure of global cognition. The domains of attention, psychomotor speed, memory, and verbal fluency were assessed in 59 participants in the Daily Trial and 19 participants in the Nocturnal Trial.We found no benefit of frequent hemodialysis in either trial for the primary cognitive outcome (Daily Trial: OR for improvement, 0.99; 95% CI, 0.59-1.66; Nocturnal Trial: OR, 1.19; 95% CI, 0.48-2.96). Similarly, there was no benefit of frequent hemodialysis in either trial on global cognition, the secondary cognitive outcome. Exploratory analyses in the Daily Trial suggested possible benefits of frequent hemodialysis for memory and verbal fluency, but not for attention and psychomotor speed. Exploratory analyses in the Nocturnal Trial suggested no benefit of frequent hemodialysis on attention, psychomotor speed, memory, or verbal fluency.Unblinded intervention, small sample.Frequent hemodialysis did not improve executive function or global cognition.

  View details for DOI 10.1053/j.ajkd.2012.09.009

  View details for Web of Science ID 000313591800009

  View details for PubMedCentralID PMC3546160

• The Association between Parathyroid Hormone Levels and Hemoglobin in Diabetic and Nondiabetic Participants in the National Kidney Foundation's Kidney Early Evaluation Program CARDIORENAL MEDICINE Memon, I., Norris, K. C., Bomback, A. S., Peralta, C., Li, S., Chen, S., McCullough, P. A., Whaley-Connell, A., Jurkovitz, C., Tamura, M. K., Saab, G. 2013; 3 (2): 120-127

  View details for DOI 10.1159/000351229

  View details for Web of Science ID 000321809200005

• 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

• Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis. Neurology Kurella Tamura, M., Meyer, J. B., Saxena, A. B., Huh, J. W., Wadley, V. G., Schiller, B. 2012; 79 (10): 981-987

  Abstract

  The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ≤ 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03-5.92) and IADL impairment (OR 3.86, 95% CI 1.60-9.28).Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.

  View details for DOI 10.1212/WNL.0b013e31826845e9

  View details for PubMedID 22875090

• Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis NEUROLOGY Tamura, M. K., Meyer, J. B., Saxena, A. B., Huh, J. W., Wadley, V. G., Schiller, B. 2012; 79 (10): 981-987

  View details for DOI 10.1212/WNL.0b013e31826845e9

  View details for Web of Science ID 000308674000012

• The IDEAL Trial: A Closer Look SEMINARS IN DIALYSIS Tamura, M. K. 2012; 25 (5): 523-525

  View details for DOI 10.1111/j.1525-139X.2012.01118.x

  View details for Web of Science ID 000308966800008

  View details for PubMedID 22823252

• Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies AMERICAN JOURNAL OF KIDNEY DISEASES Fischer, M. J., Xie, D., Jordan, N., Kop, W. J., Krousel-Wood, M., Tamura, M. K., Kusek, J. W., Ford, V., Rosen, L. K., Strauss, L., Teal, V. L., Yaffe, K., Powe, N. R., Lash, J. P. 2012; 60 (1): 27-38

  Abstract

  Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.Cross-sectional analysis.Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.Depressive symptoms measured by Beck Depression Inventory (BDI).Demographic and clinical factors.Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use.Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

  View details for DOI 10.1053/j.ajkd.2011.12.033

  View details for Web of Science ID 000305406200007

  View details for PubMedID 22497791

• Awareness of Kidney Disease and Relationship to End-stage Renal Disease and Mortality AMERICAN JOURNAL OF MEDICINE Whaley-Connell, A., Shlipak, M. G., Inker, L. A., Tamura, M. K., Bomback, A. S., Saab, G., Szpunar, S. M., McFarlane, S. I., Li, S., Chen, S., Norris, K., Bakris, G. L., McCullough, P. A. 2012; 125 (7): 661-669

  Abstract

  Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System.Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic kidney disease.Among patients identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.

  View details for DOI 10.1016/j.amjmed.2011.11.026

  View details for Web of Science ID 000305752700019

  View details for PubMedID 22626510

  View details for PubMedCentralID PMC3383388

• Timing of initiation of dialysis: time for a new direction? CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Abra, G., Tamura, M. K. 2012; 21 (3): 329-333

  Abstract

  The past 15 years have seen tremendous growth in the initiation of dialysis at higher levels of kidney function in the setting of mixed evidence and at great societal economic cost. We review recent data on the early dialysis initiation trend, the clinical and economic impact of early dialysis initiation and the future implications for the management of advanced chronic kidney disease (CKD).The percentage of patients who initiate dialysis with an estimated glomerular filtration rate (eGFR) above 10  ml/min/1.73m(2) is now greater than 50%, including 20% who initiate with an eGFR above 15 ml/min/1.73m(2). The drivers behind these findings are probably diverse but recent literature does not seem to support a higher symptom burden among the ageing CKD population as the major cause. The Initiating Dialysis Early And Late (IDEAL) trial provides guidance on the safety of waiting for symptoms or lower levels of estimated glomerular filtration rate prior to beginning dialysis. In addition, economic analyses based on the IDEAL and US Renal Data System findings suggest that significant cost savings could be achieved by reversing the early initiation trend.These findings should help clinicians and policy makers looking to rein in costs while maintaining the quality of CKD care.

  View details for DOI 10.1097/MNH.0b013e328351c244

  View details for Web of Science ID 000302769500014

  View details for PubMedID 22388556

  View details for PubMedCentralID PMC3458516

• Validation of the NINDS-CSN 5-Minute Battery for Vascular Cognitive Impairment 64th Annual Meeting of the American-Academy-of-Neurology (AAN) Kennedy, R., Wadley, V., McClure, L., Unverzagt, F., Crowe, M., Kelley, B., Nyenhuis, D., Kana, B., Marceaux, J., Tamura, M., Howard, V., Howard, G. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000303204802125

• Blood Pressure Components and End-stage Renal Disease in Persons With Chronic Kidney Disease The Kidney Early Evaluation Program (KEEP) ARCHIVES OF INTERNAL MEDICINE Peralta, C. A., Norris, K. C., Li, S., Chang, T. I., Tamura, M. K., Jolly, S. E., Bakris, G., McCullough, P. A., Shlipak, M. 2012; 172 (1): 41-47

  Abstract

  Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg).The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%).In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.

  View details for Web of Science ID 000298958900008

  View details for PubMedID 22232147

  View details for PubMedCentralID PMC3417125

• Association of Self-reported Physical Activity With Laboratory Markers of Nutrition and Inflammation: The Comprehensive Dialysis Study JOURNAL OF RENAL NUTRITION Anand, S., Chertow, G. M., Johansen, K. L., Grimes, B., Tamura, M. K., Dalrymple, L. S., Kaysen, G. A. 2011; 21 (6): 429-437

  Abstract

  Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.Between June 2005 and June 2007, CDS collected data on self-reported physical activity, nutrition, and health-related quality of life from patients starting dialysis in 296 facilities located throughout the United States. Baseline serum samples were collected from participants in a nutrition sub-study of CDS.Serum albumin and prealbumin were measured as markers of nutrition, and C-reactive protein (CRP) and α-1-acid glycoprotein as markers of inflammation. Self-reported physical activity was characterized by the maximum activity score (MAS) and adjusted activity score (AAS) of the Human Activity Profile.The mean age of participants in the analytic cohort (n = 201) was 61 years. The MAS and AAS were below the 10th and first percentile, respectively, in comparison with healthy 60 year-old norms. Both activity scores were directly correlated with albumin (r(2) = 0.3, P < .0001) and prealbumin (r(2) = 0.3, P < .0001), and inversely correlated with CRP (AAS: r(2) = -0.2, P = .01; MAS: r(2) = -0.1, P = .08). In multivariate analyses adjusting for age, gender, race/ethnicity, diabetes status, and center, both activity scores were directly correlated with prealbumin and inversely correlated with CRP.Patients new to dialysis with laboratory-based evidence of malnutrition and/or inflammation are likely to report lower levels of physical activity.

  View details for DOI 10.1053/j.jrn.2010.09.007

  View details for PubMedID 21239185

• Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study NEPHROLOGY DIALYSIS TRANSPLANTATION Anand, S., Kaysen, G. A., Chertow, G. M., Johansen, K. L., Grimes, B., Dalrymple, L. S., Tamura, M. K. 2011; 26 (11): 3683-3688

  Abstract

  As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.

  View details for DOI 10.1093/ndt/gfr098

  View details for PubMedID 21430182

• Albuminuria, kidney function, and the incidence of cognitive impairment among adults in the United States. American journal of kidney diseases Kurella Tamura, M., Muntner, P., Wadley, V., Cushman, M., Zakai, N. A., Bradbury, B. D., Kissela, B., Unverzagt, F., Howard, G., Warnock, D., McClellan, W. 2011; 58 (5): 756-763

  Abstract

  Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown.Prospective cohort study.A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study.Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit.During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ≥300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR ≥60 mL/min/1.73 m(2), eGFR <60 mL/min/1.73 m(2) was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m(2) was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend).Single measures of albuminuria and eGFR, screening test of cognition.When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.

  View details for DOI 10.1053/j.ajkd.2011.05.027

  View details for PubMedID 21816528

• Albuminuria, Kidney Function, and the Incidence of Cognitive Impairment Among Adults in the United States AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Muntner, P., Wadley, V., Cushman, M., Zakai, N. A., Bradbury, B. D., Kissela, B., Unverzagt, F., Howard, G., Warnock, D., McClellan, W. 2011; 58 (5): 756-763

  View details for DOI 10.1053/j.ajkd.2011.05.027

  View details for Web of Science ID 000296385700013

• LESS IS MORE Trends in Timing of Initiation of Chronic Dialysis in the United States ARCHIVES OF INTERNAL MEDICINE O'Hare, A. M., Choi, A. I., Boscardin, W. J., Clinton, W. L., Zawadzki, I., Hebert, P. L., Tamura, M. K., Taylor, L., Larson, E. B. 2011; 171 (18): 1663-1669

  Abstract

  During the past decade, a trend has been observed in the United States toward initiation of chronic dialysis at higher levels of estimated glomerular filtration rate. This likely reflects secular trends in the composition of the dialysis population and a tendency toward initiation of dialysis earlier in the course of kidney disease.The goal of this study was to generate model-based estimates of the magnitude of changes in the timing of dialysis initiation between 1997 and 2007. We used information from a national registry for end-stage renal disease on estimated glomerular filtration rate at initiation among patients who received their first chronic dialysis treatment in 1997 or 2007. We used information regarding predialysis estimated glomerular filtration rate slope from an integrated health care system.After accounting for changes in the characteristics of new US dialysis patients from 1997 to 2007, we estimate that chronic dialysis was initiated a mean of 147 days earlier (95% confidence interval, 134-160) in the later compared with the earlier year. Differences in timing were consistent across a range of patient subgroups but were most pronounced for those aged 75 years or older; the mean difference in timing in that subgroup was 233 days (95% confidence interval, 206-267).Chronic dialysis appears to have been initiated substantially earlier in the course of kidney disease in 2007 compared with 1997. In the absence of strong evidence to suggest that earlier initiation of chronic dialysis is beneficial, these findings call for careful evaluation of contemporary dialysis initiation practices in the United States.

  View details for Web of Science ID 000295695600012

• Correlates of insulin resistance in older individuals with and without kidney disease NEPHROLOGY DIALYSIS TRANSPLANTATION Landau, M., Kurella-Tamura, M., Shlipak, M. G., Kanaya, A., Strotmeyer, E., Koster, A., Satterfield, S., Simsonick, E. M., Goodpaster, B., Newman, A. B., Fried, L. F. 2011; 26 (9): 2814-2819

  Abstract

  Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70-79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73 m(2) 0.92, 95% confidence interval 0.87-0.98) and CKD (1.41, 1.04-1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.

  View details for DOI 10.1093/ndt/gfq817

  View details for Web of Science ID 000295231600016

  View details for PubMedID 21248294

  View details for PubMedCentralID PMC3203409

• 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

  View details for PubMedCentralID PMC4123329

• Association of Educational Attainment With Chronic Disease and Mortality: The Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Choi, A. I., Weekley, C. C., Chen, S., Li, S., Tamura, M. K., Norris, K. C., Shlipak, M. G. 2011; 58 (2): 228-234

  Abstract

  Recent reports have suggested a close relationship between education and health, including mortality, in the United States.Observational cohort.We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP).Self-reported educational attainment.Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality.We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression.Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school.Lack of income data does not allow us to disentangle the independent effects of education from income.In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups.

  View details for DOI 10.1053/j.ajkd.2011.02.388

  View details for Web of Science ID 000293010000012

  View details for PubMedID 21601328

• To Predict Dementia, Should We Be Mindful of the Kidneys? CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K. 2011; 6 (6): 1232-1234

  View details for DOI 10.2215/CJN.03390411

  View details for Web of Science ID 000291500900002

  View details for PubMedID 21566105

• Special Considerations in the Management of Chronic Kidney Disease in the Elderly DIALYSIS & TRANSPLANTATION Cheung, K. L., Soman, S., Tamura, M. K. 2011; 40 (6): 241-243

  View details for DOI 10.1002/dat.20571

  View details for Web of Science ID 000291561300004

  View details for PubMedCentralID PMC3142958

• Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Risk Factors for and Complications of CKD and Mortality in the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES Stevens, L. A., Li, S., Tamura, M. K., Chen, S., Vassalotti, J. A., Norris, K. C., Whaley-Connell, A. T., Bakris, G. L., McCullough, P. A. 2011; 57 (3): S9-S16

  Abstract

  The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m(2). Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.The prevalence of eGFR(CKD-EPI) <60 mL/min/1.73 m(2) was 14.3% compared with 16.8% using eGFR(MDRD). Using eGFR(CKD-EPI), 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m(2) using both equations, those with eGFR(CKD-EPI) of 60-89 mL/min/1.73 m(2) had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.

  View details for DOI 10.1053/j.ajkd.2010.11.007

  View details for Web of Science ID 000287472800003

  View details for PubMedID 21338849

  View details for PubMedCentralID PMC3298760

• Comparison of CKD Awareness in a Screening Population Using the Modification of Diet in Renal Disease (MDRD) Study and CKD Epidemiology Collaboration (CKD-EPI) Equations AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Anand, S., Li, S., Chen, S., Whaley-Connell, A. T., Stevens, L. A., Norris, K. C. 2011; 57 (3): S17-S23

  View details for DOI 10.1053/j.ajkd.2010.11.008

  View details for Web of Science ID 000287472800004

• Comparison of CKD awareness in a screening population using the Modification of Diet in Renal Disease (MDRD) study and CKD Epidemiology Collaboration (CKD-EPI) equations. American journal of kidney diseases Kurella Tamura, M., Anand, S., Li, S., Chen, S., Whaley-Connell, A. T., Stevens, L. A., Norris, K. C. 2011; 57 (3): S17-23

  Abstract

  Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.In this cross-sectional study, we used data collected from 2000-2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.Of 26,213 participants with CKD based on GFR estimated using the MRDR equation (eGFR(MDRD)), 23,572 (90%) also were classified with CKD based on eGFR(CKD-EPI). Based on eGFR(MDRD), 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with stages 1-5, respectively. Based on eGFR(CKD-EPI), 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with stages 1-5, respectively. Reclassification to a less advanced CKD stage using eGFR(CKD-EPI) was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFR(CKD-EPI).Using eGFR(CKD-EPI) led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.

  View details for DOI 10.1053/j.ajkd.2010.11.008

  View details for PubMedID 21338846

• Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Prevalence of and Risk Factors for Diabetes Mellitus in CKD in the Kidney Early Evaluation Program (KEEP) AMERICAN JOURNAL OF KIDNEY DISEASES McFarlane, S. I., McCullough, P. A., Sowers, J. R., Soe, K., Chen, S., Li, S., Vassalotti, J. A., Stevens, L. A., Salifu, M. O., Tamura, M. K., Bomback, A. S., Norris, K. C., Collins, A. J., Bakris, G. L., Whaley-Connell, A. T. 2011; 57 (3): S24-S31

  Abstract

  Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown.This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations.CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14).Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.

  View details for DOI 10.1053/j.ajkd.2010.11.009

  View details for Web of Science ID 000287472800005

  View details for PubMedID 21338847

  View details for PubMedCentralID PMC3237700

• Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Xie, D., Yaffe, K., Cohen, D. L., Teal, V., Kasner, S. E., Messe, S. R., Sehgal, A. R., Kusek, J., DeSalvo, K. B., Cornish-Zirker, D., Cohan, J., Seliger, S. L., Chertow, G. M., Go, A. S. 2011; 6 (2): 248-256

  Abstract

  Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

  View details for DOI 10.2215/CJN.02660310

  View details for PubMedID 20930087

• Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies KIDNEY INTERNATIONAL Tamura, M. K., Yaffe, K. 2011; 79 (1): 14-22

  View details for DOI 10.1038/ki.2010.336

  View details for Web of Science ID 000285334100004

• Special considerations in the management of chronic kidney disease in the elderly. Dialysis & transplantation Cheung, K. L., Soman, S., Tamura, M. K. 2011; 40 (6): 241–43

  View details for PubMedID 21799548

  View details for PubMedCentralID PMC3142958

• Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney international Kurella Tamura, M., Yaffe, K. 2011; 79 (1): 14-22

  Abstract

  Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment.

  View details for DOI 10.1038/ki.2010.336

  View details for PubMedID 20861818

• Design and Rationale of Health-Related Quality of Life and Patient-Reported Outcomes Assessment in the Frequent Hemodialysis Network Trials 13th International Conference on Dialysis, Advances Jhamb, M., Tamura, M. K., Gassman, J., Garg, A. X., Lindsay, R. M., Suri, R. S., Ting, G., Finkelstein, F. O., Beach, S., Kimmel, P. L., Unruh, M. KARGER. 2011: 151–58

  Abstract

  End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important.The aim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials.In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients' self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden.Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.

  View details for DOI 10.1159/000321855

  View details for Web of Science ID 000287667000026

  View details for PubMedID 21228584

• The Association between Parathyroid Hormone Levels and the Cardiorenal Metabolic Syndrome in Non-Diabetic Chronic Kidney Disease CARDIORENAL MEDICINE Saab, G., Whaley-Connell, A., Bombeck, A., Tamura, M. K., Li, S., Chen, S., McFarlane, S. I., Sowers, J. R., Norris, K., Bakris, G. L., McCullough, P. A. 2011; 1 (2): 123-130

  View details for DOI 10.1159/000327149

  View details for Web of Science ID 000312167400006

• Impact of Sleep Quality on Cardiovascular Outcomes in Hemodialysis Patients: Results from the Frequent Hemodialysis Network Study AMERICAN JOURNAL OF NEPHROLOGY Unruh, M., Tamura, M. K., Larive, B., Rastogi, A., James, S., Schiller, B., Gassman, J., Chan, C., Lockridge, R., Kliger, A. 2011; 33 (5): 398-406

  View details for DOI 10.1159/000326343

  View details for Web of Science ID 000290841100003

• Signs and Symptoms Associated With Earlier Dialysis Initiation in Nursing Home Residents AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., O'Hare, A. M., McCulloch, C. E., Johansen, K. L. 2010; 56 (6): 1117-1126

  Abstract

  Factors driving the trend of earlier dialysis initiation for persons with end-stage renal disease are unknown. We wanted to determine the association of the number and type of signs and symptoms with timing of initiation of dialysis in US nursing home residents.Observational study.We used data from the US Renal Data System linked with the Minimum Data Set, a national registry of nursing home residents. The cohort consisted of 2,402 nursing home residents who initiated dialysis between 1998 and 2000 and had at least 2 recorded clinical assessments in the year before dialysis initiation.We evaluated 7 clinical signs and symptoms: dependence in activities of daily living, cognitive function, edema, dyspnea, nutritional problems, vomiting, and body size.Earlier dialysis initiation was defined as estimated glomerular filtration rate ≥ 1 5 mL/min/1.73 m² at the start of dialysis.Median estimated glomerular filtration rate at the start of dialysis was 9.8 (25th-75th percentile, 7.4-13.4) mL/min/1.73 m². After adjustment for age, sex, race, and comorbid conditions, each additional sign or symptom was associated with a higher odds for earlier dialysis initiation (OR, 1.16 per symptom; 95% CI, 1.06-1.28), as was each adversely changing sign or symptom (OR, 1.26 per symptom; 95% CI, 1.16-1.38). The population-attributable risk for earlier dialysis initiation associated with having one or more signs and symptoms of volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss was 31%; volume overload had the largest aggregate population-attributable risk.We lacked information about metabolic indications for dialysis initiation.Volume overload, cognitive decline, increasing activities of daily living dependence, and weight loss were associated with earlier dialysis initiation; however, these factors explained less than one-third of cases of earlier dialysis initiation in nursing home residents.

  View details for DOI 10.1053/j.ajkd.2010.08.017

  View details for Web of Science ID 000284401800016

  View details for PubMedID 20974509

• Hemoglobin Concentration and Cognitive Impairment in the Renal REasons for Geographic And Racial Differences in Stroke (REGARDS) Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Kurella Tamura, M., Wadley, V. G., Newsome, B. B., Zakai, N. A., McClure, L. A., Howard, G., Warnock, D. G., McClellan, W. 2010; 65 (12): 1380-1386

  Abstract

  There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults.We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women).The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ≥2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ≥2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94-2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race.Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment.

  View details for DOI 10.1093/gerona/glq126

  View details for Web of Science ID 000284639700014

  View details for PubMedID 20634281

• Should there be an expanded role for palliative care in end-stage renal disease? CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Tamura, M. K., Cohen, L. M. 2010; 19 (6): 556-560

  Abstract

  In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation.Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently. Furthermore, although hospice care is associated with improved symptom control and lower healthcare costs at the end of life, it is underutilized by the ESRD population, even among patients who withdraw from dialysis. A palliative care model incorporating communication of prognosis, advance care planning, symptom assessment and management, and timely hospice referral may improve quality of life and quality of dying. Resources and clinical practice guidelines are available to assist practitioners with incorporating palliative care into ESRD management.There is a large unmet need to alleviate the physical, psychosocial, and existential suffering of patients with ESRD. More fully integrating palliative care into ESRD management by improving end-of-life care training, eliminating structural and financial barriers to hospice use, and identifying optimal methods to deliver palliative care are necessary if we are to successfully address the needs of an aging ESRD population.

  View details for DOI 10.1097/MNH.0b013e32833d67bc

  View details for Web of Science ID 000282981200007

  View details for PubMedID 20644475

• Prevalence and Correlates of Cognitive Impairment in Hemodialysis Patients: The Frequent Hemodialysis Network Trials CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Tamura, M. K., Larive, B., Unruh, M. L., Stokes, J. B., Nissenson, A., Mehta, R. L., Chertow, G. M. 2010; 5 (8): 1429-1438

  Abstract

  Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications.Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors.Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors.

  View details for DOI 10.2215/CJN.01090210

  View details for PubMedID 20576825

• The elderly patients on hemodialysis. Minerva urologica e nefrologica = The Italian journal of urology and nephrology Anand, S., Kurella Tamura, M., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for PubMedID 20424572

• The elderly patients on hemodialysis MINERVA UROLOGICA E NEFROLOGICA Anand, S., Tamura, M. K., Chertow, G. M. 2010; 62 (1): 87-101

  Abstract

  Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

  View details for Web of Science ID 000208661300008

• Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Yaffe, K., Ackerson, L., Tamura, M. K., Le Blanc, P., Kusek, J. W., Sehgal, A. R., Cohen, D., Anderson, C., Appel, L., DeSalvo, K., Ojo, A., Seliger, S., Robinson, N., Makos, G., Go, A. S. 2010; 58 (2): 338-345

  Abstract

  To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors.Cross-sectional.Chronic Renal Insufficiency Cohort Study.Eight hundred twenty-five adults aged 55 and older with CKD.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean).Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59).In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

  View details for DOI 10.1111/j.1532-5415.2009.02670.x

  View details for Web of Science ID 000274183800017

  View details for PubMedID 20374407

  View details for PubMedCentralID PMC2852884

• Preferences for dialysis withdrawal and engagement in advance care planning within a diverse sample of dialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Tamura, M. K., Goldstein, M. K., Perez-Stable, E. J. 2010; 25 (1): 237-242

  Abstract

  Rates of dialysis withdrawal are higher among the elderly and lower among Blacks, yet it is unknown whether preferences for withdrawal and engagement in advance care planning also vary by age and race or ethnicity. DESIGN, SETTING, PARTICIPANTS AND METHODS: We recruited 61 participants from two dialysis clinics to complete questionnaires regarding dialysis withdrawal preferences in five different health states. Engagement in advance care planning (end-of-life discussions), completion of advance directives and 'do not resuscitate' or 'do not intubate' (DNR/DNI) orders were ascertained by a questionnaire and from dialysis unit records.The mean age was 62 +/- 15 years; 38% were Black, 11% were Latino, 34% were White and 16% of participants were Asian. Blacks were less likely to prefer dialysis withdrawal as compared with Whites (odds ratio 0.16, 95% confidence interval 0.03-0.88) and other race/ethnicity groups, and this difference was not explained by age, education, comorbidity and other confounders. In contrast, older age was not associated with preferences for withdrawal. Rates of engagement in end-of-life discussions were higher than for documentation of advance care planning for all age and most race/ethnicity groups. Although younger participants and minorities were generally less likely to document treatment preferences as compared with older patients and Whites, they were not less likely to engage in end-of-life discussions.Preferences for withdrawal vary by race/ ethnicity, whereas the pattern of engagement in advance care planning varies by age and race/ethnicity. Knowledge of these differences may be useful for improving communication about end-of-life preferences and in implementing effective advance care planning strategies among diverse haemodialysis patients.

  View details for DOI 10.1093/ndt/gfp430

  View details for Web of Science ID 000273113100039

  View details for PubMedID 19734137

  View details for PubMedCentralID PMC2910327

• Frailty and Chronic Kidney Disease: The Third National Health and Nutrition Evaluation Survey AMERICAN JOURNAL OF MEDICINE Wilhelm-Leen, E. R., Hall, Y. N., Tamura, M. K., Chertow, G. M. 2009; 122 (7): 664-U86

  Abstract

  Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive.

  View details for DOI 10.1016/j.amjmed.2009.01.026

  View details for PubMedID 19559169

• Incidence, management, and outcomes of end-stage renal disease in the elderly CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Tamura, M. K. 2009; 18 (3): 252-257

  Abstract

  The elderly constitute a substantial and growing fraction of the end-stage renal disease (ESRD) population. We review recent studies on ESRD incidence, management, and outcomes in the elderly.Rates of treated ESRD among the elderly (>80 years) have risen by more than 50% in the last decade. In studies with a large number of elderly patients, median survival after dialysis initiation is modest, and although a majority have reasonable life expectancy, a substantial minority of elderly patients experience very high early mortality rates after dialysis initiation. Quality of life results are mixed--compared with younger ESRD patients or non-ESRD elderly, mental well being is similar and physical well being is reduced in elderly patients with ESRD. In several studies, elderly patients with ESRD initiating peritoneal dialysis had higher mortality rates than elderly patients with ESRD initiating hemodialysis. Strategies such as nondialytic management of ESRD or dietary protein restriction and delayed dialysis initiation may be alternatives for elderly patients wishing to avoid dialysis initiation, but further studies are needed to determine the patients best suited for these approaches. Quality improvement initiatives in geriatric ESRD care have been successfully implemented in some centers and may ultimately improve care for elderly patients with ESRD.These findings should help to clarify some of the risks and benefits of dialysis in the elderly and may be useful in dialysis decision-making and management.

  View details for DOI 10.1097/MNH.0b013e328326f3ac

  View details for Web of Science ID 000265560600011

  View details for PubMedID 19374012

• Kidney function and cognitive impairment in US adults: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study AMERICAN JOURNAL OF KIDNEY DISEASES Tamura, M. K., Wadley, V., Yaffe, K., McClure, L. A., Howard, G., Go, R., Allman, R. M., Warnock, D. G., McClellan, W. 2008; 52 (2): 227-234

  Abstract

  The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity.Cross-sectional.23,405 participants (mean age, 64.9 +/- 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample.Estimated glomerular filtration rate (eGFR).Cognitive impairment.Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m(2). Kidney function was analyzed in 10-mL/min/1.73 m(2) increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment.CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m(2) decrease in eGFR less than 60 mL/min/1.73 m(2) was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m(2) or greater.Longitudinal measures of cognitive function were not available.In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD.

  View details for DOI 10.1053/j.ajkd.2008.05.004

  View details for Web of Science ID 000257943400007

  View details for PubMedID 18585836

• Cystatin C as a marker of cognitive function in elders: Findings from the Health ABC study ANNALS OF NEUROLOGY Yaffe, K., Lindquist, K., Shlipak, M. G., Simonsick, E., Fried, L., Rosano, C., Satterfield, S., Atkinson, H., Windham, B. G., Kurella-Tamura, M. 2008; 63 (6): 798-802

  Abstract

  We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).

  View details for DOI 10.1002/ana.21383

  View details for Web of Science ID 000257294100014

  View details for PubMedID 18496846

• Kidney function as a predictor of loss of lean mass in older adults: Health, aging and body composition study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Fried, L. F., Boudreau, R., Lee, J. S., Chertow, G., Kurella-Tamura, M., Shlipak, M. G., Ding, J., Sellmeyer, D., Tylavsky, F. A., Simsonick, E., Kritchevsky, S. B., Harris, T. B., Newman, A. B. 2007; 55 (10): 1578-1584

  Abstract

  To assess the association between kidney function and change in body composition in older individuals.Prospective cohort study.Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee.Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study.Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis.High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (-0.07+/-0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (-0.05+/-0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (-0.19+/-0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change.Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences.

  View details for DOI 10.1111/j.1532-5415.2007.01398.x

  View details for Web of Science ID 000249825500011

  View details for PubMedID 17908060

• Correlates and outcomes of dementia among dialysis patients: the Dialysis Outcomes and Practice Patterns Study NEPHROLOGY DIALYSIS TRANSPLANTATION Kurella, M., Mapes, D. L., Port, F. K., Chertow, G. M. 2006; 21 (9): 2543-2548

  Abstract

  Recent studies suggest a high prevalence of cognitive impairment and dementia in persons with end-stage renal disease (ESRD), yet risk factors for dementia and its prognostic significance in persons with ESRD remain unclear. The goals of this study were to determine the prevalence, correlates and dialysis-related outcomes of dementia in an international sample of haemodialysis patients.We analysed data collected from a cohort of 16 694 patients in the Dialysis Outcomes and Practice Patterns Study. Dementia was defined as a diagnosis of dementia documented in the medical record. We used logistic regression to determine the baseline correlates of dementia and Cox proportional hazards models to determine the relative risk (RR) of death and dialysis withdrawal for patients with dementia, while adjusting for a number of confounding factors.Overall, 4% of the cohort had a recorded diagnosis of dementia. In the cross-sectional analyses, risk factors for dementia in the general population including age, black race, low educational attainment, cerebrovascular disease and diabetes, as well as modifiable uraemia-related factors, including markers of malnutrition and anaemia, were independently associated with dementia. After adjustment for a number of confounding factors, dementia was associated with an increased risk of death [RR 1.48, 95% confidence interval (CI) 1.32-1.66] and dialysis withdrawal (RR 2.01, 95% CI 1.57-2.57).Dementia is associated with adverse outcomes among ESRD patients. Dialysis providers should consider instituting routine screening for cognitive impairment among elderly patients in order to identify those at risk for associated adverse outcomes.

  View details for DOI 10.1093/ndt/gfl275

  View details for Web of Science ID 000240694200032

  View details for PubMedID 16751655

• The tortoise and hare on hemodialysis: Does slow and steady win the race? KIDNEY INTERNATIONAL Chertow, G. M., Kurella, M., Lowrie, E. G. 2006; 70 (1): 24-25

  Abstract

  The importance of hemodialysis session length relative to small solute (e.g., urea) clearance has been debated for many years. Longer session length augments clearance of larger molecules and may facilitate ultrafiltration; however, the independent effects of session length on survival and other outcomes are unknown. In this report, we review two recently published observational studies examining the association between hemodialysis session length and survival. Prospective clinical trials will be required to resolve the debate.

  View details for DOI 10.1038/sj.ki.5001544

  View details for Web of Science ID 000238969300012

  View details for PubMedID 16763569

• The metabolic syndrome and chronic kidney disease CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Peralta, C. A., Kurella, M., Lo, J. C., Chertow, G. M. 2006; 15 (4): 361-365

  Abstract

  The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease.A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors.The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

  View details for Web of Science ID 000239103000002

  View details for PubMedID 16775449

• Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Bretz, W. A., Weyant, R. J., Corby, P. M., Ren, D., Weissfeld, L., Kritchevsky, S. B., Harris, T., Kurella, M., Satterfield, S., Visser, M., Newman, A. B. 2005; 53 (9): 1532-1537

  Abstract

  To study the levels of systemic markers for inflammation with parameters of periodontal diseases in older people.A cross-sectional study was conducted in a cohort that is being followed prospectively on the effects of aging and body composition on morbidity.University of Pittsburgh, Pittsburgh, and University of Tennessee, Memphis.One thousand one hundred thirty-one participants (mean age+/-standard deviation 72.7+/-2.8); 66% white and 50% male.Periodontal examination, including probing depth and attachment loss, was performed. Periodontal disease extent was divided into 0% of sites with probing depth of 6 mm or more, 1% to 10% of sites with probing depth of 6 mm or more and more than 10% of sites with probing depth of 6 mm or more. Subgingival plaque samples were collected from four molar teeth, and the levels of periodontal pathogens were determined using the benzoyl-DL-arginine-naphthylamide (BANA) test. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), and tumor necrosis factor alpha (TNF-alpha) levels were measured in all participants. Assessments of risk factors associated with elevated levels of markers of systemic inflammation were also determined. Multiple regression analysis was employed to analyze the data.IL-6 levels were significantly higher in participants with more-extensive periodontal disease than in other participants. Periodontal disease extent was significantly associated with higher TNF-alpha plasma levels, controlling for established risk factors for elevated TNF-alpha levels. Participants with BANA-positive species had significantly higher CRP plasma levels when controlling for risk factors for elevated CRP levels.Periodontal disease and infection may be modifiable risk indicators for elevated levels of systemic inflammatory markers in older people.

  View details for DOI 10.1111/j.1532-5415.2005.53468.x

  View details for Web of Science ID 000231509000012

  View details for PubMedID 16137283

• Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Chertow, G. M., Fried, L. F., Cummings, S. R., Harris, T., Simonsick, E., Satterfield, S., Ayonayon, H., Yaffe, K. 2005; 16 (7): 2127-2133

  Abstract

  Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

  View details for Web of Science ID 000230046900032

  View details for PubMedID 15888561

• Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Lo, J. C., Chertow, G. M. 2005; 16 (7): 2134-2140

  Abstract

  The metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease; however, no prospective studies have examined the metabolic syndrome as a risk factor for chronic kidney disease (CKD). A total of 10,096 nondiabetic participants who were in the Atherosclerosis Risk in Communities study and had normal baseline kidney function composed the study cohort. The metabolic syndrome was defined according to recent guidelines from the National Cholesterol Education Program. Incident CKD was defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2 at study year 9 among those with an eGFR > or =60 ml/min per 1.73 m2 at baseline. After 9 yr of follow-up, 691 (7%) participants developed CKD. The multivariable adjusted odds ratio (OR) of developing CKD in participants with the metabolic syndrome was 1.43 (95% confidence interval [CI], 1.18 to 1.73). Compared with participants with no traits of the metabolic syndrome, those with one, two, three, four, or five traits of the metabolic syndrome had OR of CKD of 1.13 (95% CI, 0.89 to 1.45), 1.53 (95% CI, 1.18 to 1.98), 1.75 (95% CI, 1.32 to 2.33), 1.84 (95% CI, 1.27 to 2.67), and 2.45 (95% CI, 1.32 to 4.54), respectively. After adjusting for the subsequent development of diabetes and hypertension during the 9 yr of follow-up, the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51). The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults.

  View details for Web of Science ID 000230046900033

  View details for PubMedID 15901764

• Dialysis session length ("t") as a determinant of the adequacy of dialysis SEMINARS IN NEPHROLOGY Kurella, M., Chertow, G. M. 2005; 25 (2): 90-95

  Abstract

  Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increased risk for morbidity and mortality, independent of the time-averaged concentration of urea. Observational studies of dialysis session length have yielded conflicting results, although virtually all studies have confounded hemodialysis session length with hemodialysis efficiency or dose. Limited observational data from nocturnal hemodialysis programs more strongly suggest an independent beneficial effect of longer session length. In aggregate, data on the effects of hemodialysis session length are inconclusive. Future studies should evaluate hemodialysis session length independent of efficiency, and should consider the evaluation of dose by using other clearance parameters and the adequacy of ultrafiltration in addition to solute kinetics.

  View details for DOI 10.1016/j.semnephrol.2004.09.015

  View details for Web of Science ID 000228545200005

  View details for PubMedID 15791560

• Suicide in the United States end-stage renal disease program JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Kimmel, P. L., Young, B. S., Chertow, G. M. 2005; 16 (3): 774-781

  Abstract

  Although depression and dialysis withdrawal are relatively common among individuals with ESRD, there have been few systematic studies of suicide in this population. The goals of this study were to compare the incidence of suicide with national rates and to contrast the factors associated with suicide with those associated with withdrawal in persons with ESRD. All individuals who were aged 15 yr and older and initiated dialysis between April 1, 1995, and November 30, 2000, composed the analytic cohort. Patients were censored at the time of death, transplantation, or October 31, 2001. Death as a result of suicide in the ESRD population and the general US population was ascertained from the Death Notification Form and the Centers for Disease Control and Prevention, respectively. Standardized incidence ratios for suicide among patient subgroups were computed using national data from the year 2000 as the reference population. The crude suicide rate from 1995 to 2001 was 24.2 suicides per 100,000 patient-years, and the overall standardized incidence ratio for suicide was 1.84 (95% confidence interval, 1.50 to 2.27). In multivariable models, age > or =75 yr, male gender, white or Asian race, geographic region, alcohol or drug dependence, and recent hospitalization with mental illness were significant independent predictors of death as a result of suicide. Persons with ESRD are significantly more likely to commit suicide than persons in the general population. Although relatively rare, risk assessment can be used to identify patients for whom counseling and other interventions might be beneficial.

  View details for DOI 10.1681/ASN.2004070550

  View details for Web of Science ID 000227372000026

  View details for PubMedID 15659561

• Frequent hemodialysis and psychosocial function SEMINARS IN DIALYSIS Kurella, M., Suri, R. S., Chertow, G. M. 2005; 18 (2): 132-136

  Abstract

  Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.

  View details for Web of Science ID 000227478200010

  View details for PubMedID 15771657

• Self-assessed sleep quality in chronic kidney disease. International urology and nephrology Kurella, M., Luan, J., Lash, J. P., Chertow, G. M. 2005; 37 (1): 159-165

  Abstract

  Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease.We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep.Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01).Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

  View details for PubMedID 16132780

• Chronic kidney disease and cognitive impairment in menopausal women AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Yaffe, K., Shlipak, M. G., Wenger, N. K., Chertow, G. M. 2005; 45 (1): 66-76

  Abstract

  Although end-stage renal disease has been associated with cognitive impairment, the relation between lesser degrees of chronic kidney disease (CKD) and cognitive impairment is less well understood.Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed. All participants were younger than 80 years and had established coronary artery disease at study entry. Participants underwent 6 standard tests of cognitive function evaluating various domains. Unadjusted, residual age- and race-adjusted, and multivariable-adjusted linear and logistic regression models were used. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFRs, CKD was categorized as mild (estimated GFR [eGFR], 45 to 60 mL/min/1.73 m2), moderate (eGFR, 30 to 44 mL/min/1.73 m2), and severe (eGFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean eGFR was 57 +/- 14 mL/min/1.73 m2. In multivariable analyses, eGFR was associated significantly with impairment in global cognition, executive function, language, and memory (approximately 15% to 25% increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR). Associations among eGFR and cognitive function were independent of residual effects of age and race (2 key determinants of GFR) and the contributions of education, lifestyle factors, stroke, diabetes, and other laboratory variables.CKD is associated with cognitive impairment in menopausal women with coronary artery disease.

  View details for DOI 10.1053/j.ajkd.2004.08.044

  View details for Web of Science ID 000226517300009

  View details for PubMedID 15696445

• Validation of the kidney disease quality of life (KDQOL) cognitive function subscale KIDNEY INTERNATIONAL Kurella, M., Luan, J., Yaffe, K., Chertow, G. M. 2004; 66 (6): 2361-2367

  Abstract

  Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease.We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves.Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores.The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

  View details for Web of Science ID 000225026200028

  View details for PubMedID 15569327

• Cognitive impairment in chronic kidney disease JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Kurella, M., Chertow, G. M., Luan, J., Yaffe, K. 2004; 52 (11): 1863-1869

  Abstract

  To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.Cross-sectional study.University-affiliated ambulatory nephrology and dialysis practices.Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3.Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation.There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function.Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.

  View details for Web of Science ID 000224594100010

  View details for PubMedID 15507063

• Physical and sexual function in women with chronic kidney disease AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Ireland, C., Hlatky, M. A., Shlipak, M. G., Yaffe, K., Hulley, S. B., Chertow, G. M. 2004; 43 (5): 868-876

  Abstract

  Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown.To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines.Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function.CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

  View details for DOI 10.1053/j.ajkd.2003.12.050

  View details for Web of Science ID 000221104800013

  View details for PubMedID 15112178

• Analgesia in patients with ESRD: A review of available evidence AMERICAN JOURNAL OF KIDNEY DISEASES Kurella, M., Bennett, W. M., Chertow, G. M. 2003; 42 (2): 217-228

  Abstract

  Moderate to severe pain frequently accompanies chronic diseases in general and end-stage renal disease (ESRD) in particular. Several analgesic agents and associated metabolites show altered pharmacokinetics in the presence of reduced glomerular filtration rate. Drug-related side effects may exacerbate symptoms frequently observed in persons with chronic kidney disease (CKD; eg, fatigue, nausea, vomiting, and constipation) or those often attributed to hemodialysis therapy (eg, orthostatic hypotension and impaired cognition). Persons with advanced CKD and ESRD are at increased risk for adverse effects of analgesic agents because of enhanced drug sensitivity, comorbid conditions, and concurrent medication use. Dose adjustment and avoidance of certain analgesics may be required in patients with advanced CKD and ESRD. We review the available evidence on pharmacokinetics and adverse drug effects of various analgesic agents commonly used in patients with advanced CKD and ESRD. Determining an optimal approach to the control of pain in patients with advanced CKD and ESRD will require additional research.

  View details for DOI 10.1016/S0272-6386(03)00645-0

  View details for Web of Science ID 000184557300001

  View details for PubMedID 12900801

• Post transplant erythrocytosis in hypercalcernic renal transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Kurella, M., Butterly, D. W., Smith, S. R. 2003; 3 (7): 873-877

  Abstract

  In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.

  View details for Web of Science ID 000184032600013

  View details for PubMedID 12814479

• Monitoring changes in gene expression in renal ischemia-reperfusion in the rat KIDNEY INTERNATIONAL Yoshida, T., Kurella, M., Beato, F., Min, H., Ingelfinger, J. R., Stears, R. L., Swinford, R. D., Gullans, S. R., Tang, S. S. 2002; 61 (5): 1646-1654

  Abstract

  Although acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality, its molecular basis remains incompletely defined. The present study examined global gene expression in the well-characterized ischemia-reperfusion model of ARF using DNA microarray technology.Male Wistar rats underwent bilateral renal ischemia (30 min) or sham operation, followed by reperfusion for 1, 2, 3 or 4 days. Plasma creatinine increased approximately fivefold over baseline, peaking on day 1. Renal total RNA was used to probe cDNA microarrays.Alterations in expression of 18 genes were identified by microarray analysis. Nine genes were up-regulated (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1, fibronectin, heat-responsive protein 12 and FK506 binding protein in the established phase), whereas another nine were down-regulated (glutamine synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14, Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established phase). The identities of these 18 genes were sequence-verified. Changes in gene expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and PPARgamma have not previously been known to be involved in ARF.Using DNA microarray technology, we identified changes in expression of 18 genes during renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR. Several genes, not previously been identified as playing a role in ischemic ARF, may have importance in this disease.

  View details for Web of Science ID 000175054200009

  View details for PubMedID 11967014

• DNA microarray analysis of complex biologic processes JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kurella, M., Hsiao, L. L., Yoshida, T., Randall, J. D., Chow, G., Sarang, S. S., Jensen, R. V., Gullans, S. R. 2001; 12 (5): 1072-1078

  Abstract

  DNA microarrays, or gene chips, allow surveys of gene expression, (i.e., mRNA expression) in a highly parallel and comprehensive manner. The pattern of gene expression produced, known as the expression profile, depicts the subset of gene transcripts expressed in a cell or tissue. At its most fundamental level, the expression profile can address qualitatively which genes are expressed in disease states. However, with the aid of bioinformatics tools such as cluster analysis, self-organizing maps, and principle component analysis, more sophisticated questions can be answered. Microarrays can be used to characterize the functions of novel genes, identify genes in a biologic pathway, analyze genetic variation, and identify therapeutic drug targets. Moreover, the expression profile can be used as a tissue or disease "fingerprint." This review details the fabrication of arrays, data management tools, and applications of microarrays to the field of renal research and the future of clinical practice.

  View details for Web of Science ID 000168307600024

  View details for PubMedID 11316867