Bio

Clinical Focus


  • Amyloidosis
  • Glomerular Disease
  • Nephrology
  • Nephrology (Kidney)
  • Kidney and Pancreas Transplantation

Academic Appointments


Administrative Appointments


  • Director, Stanford Glomerular DIsease Center (2010 - Present)
  • Clinical Chief, Nephrology, Stanford University (1999 - 2012)
  • Associate Chair, Stanford University School of Medicine - Medicine (2002 - 2007)

Professional Education


  • Residency:Long Island Jewish Medical Center (1988) NY
  • Fellowship:Stanford University School of Medicine (1992) CA
  • Board Certification: Nephrology, American Board of Internal Medicine (1990)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1988)
  • Internship:Long Island Jewish Medical Center (1986) NY
  • Medical Education:New York Medical College (1985) NY

Research & Scholarship

Current Research and Scholarly Interests


We are continuing to grow a glomerulonephritis cohort study, including immunologic characterization. We have completed interventional studies of preeclampsia exploring the nitric oxide, endothelin system and effects on glomerular function and morphometry. We continue to recruit patients for treatment and observational studies of glomerular disease, including FSGS, membranous and particularly IgA nephropathy. We also are actively studying renal disease in systemic amyloidosis.

Clinical Trials


  • Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH Not Recruiting

    FSGS is an immunologic disorder wherein circulating immune proteins cause damage to the kidneys and progressive injury and scarring. Corticosteroid therapy is occasionally, but not nearly universally, successful in reducing proteinuria, and when patients respond, they have a favorable prognosis. The investigators believe that ACTH therapy (H.P. Acthar Gel) can provide a more rapid, well tolerated reduction in glomerular injury.

    Stanford is currently not accepting patients for this trial. For more information, please contact Richard Lafayette, (650) 723-6248.

    View full details

  • Nephrotic Syndrome Study Network Recruiting

    Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients. In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium. Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.

    View full details

  • Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy Recruiting

    Background: - Membranous nephropathy is associated with damage to the walls of the glomeruli, the small blood vessels in the kidneys that filter waste products from the blood. This damage causes leakage of blood proteins into the urine and is associated with low blood protein levels, high blood cholesterol values, and swelling of the legs. These problems can decrease or go away without treatment in about 25 percent of patients, but if they persist, some patients may experience impaired (or loss of) kidney function, blood vessel and heart disease, and a risk of forming blood clots in veins. - Kidney biopsies that show that antibodies have been deposited along the glomeruli suggest that specialized cells of the immune system, called B and T cells, are causing damage to the kidneys through their increased activity. To suppress the action of B and T cells and to decrease the harmful deposits in the kidneys, drug treatments are required. - Patients with membranous nephropathy are often treated with immunosuppressive drugs such as cyclosporine or cytoxan plus steroids that attempt to reduce or suppress the activity of the immune system, decrease antibody production, and reduce antibody deposits in the kidney. However, not everyone responds to these medications and the kidney disease can return in some patients when the drugs are stopped. Also, there are side effects associated with long term usage of these medications. Rituximab, a different immunosuppressant, has also been used for this purpose. Although cyclosporine and Rituximab have been used separately, they have not been tried in combination as a possible treatment for membranous nephropathy. Objectives: - To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy. Eligibility: - Individuals 18 years of age and older who have been diagnosed with membranous nephropathy based on a kidney biopsy done within the preceding 24 months, and who have had excess levels of protein in the urine for at least 6 months based on urine and blood tests. Design: - Potential participants will be screened with an initial clinic evaluation and full medical history. - Before the treatment, there will be a run-in period that will last up to 2 months. During this time, participants will be placed on a blood pressure lowering medication and will not take any other immunosuppressant medications. - Participants will visit the NIH clinical center for a baseline evaluation, four intravenous infusions of rituximab, and also at 1- to 6-month intervals throughout the study. - Active treatment period will involve a 6-month course of cyclosporine and a total of four doses of rituximab. Participants will take cyclosporine tablets twice daily, and have two infusions of rituximab given 2 weeks apart, After 6 months, the cyclosporine dose will slowly be decreased over several weeks and then completely discontinued. Participants will then receive another course (two doses 2 weeks apart) of rituximab, depending on results of blood work. - Participants will have frequent blood and urine tests performed to monitor the results of treatment and reduce the chance of side effects.

    View full details

  • Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients Recruiting

    The purpose of this study is to provide nephrologists with additional clinical evidence regarding the efficacy and safety of Acthar in subjects with treatment-resistant idiopathic membranous nephropathy. Approximately sixty (60) subjects will be randomized in this double-blind, parallel-group, placebo-controlled, multicenter study comparing Acthar and Placebo administered 2 times per week for a 24-week treatment period followed by a 24-week observation period. The primary objective of this study is to assess the proportion of treatment-resistant subjects (defined as subjects who either have had no response or have suffered a relapse after achieving a partial response to their most recent standard treatment regimen) who have a complete or partial remission of proteinuria in nephrotic syndrome due to idiopathic membranous nephropathy after 24 weeks of treatment.

    View full details

  • Rituximab in Progressive IgA Nephropathy Recruiting

    Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, we speculate that the reduction of circulating IgA may reduce proteinuria and injury in patients with IgA nephropathy. Moreover, the absence of prospective trials in the treatment of IgA disease and the lack of consensus for long-term treatment, the superior side-effect profile of this form of therapy may lead to significant advances in the treatment of this prevalent from of glomerulonephritis.

    View full details

  • Belimumab in Remission of VASculitis Recruiting

    The purpose of this study is to evaluate the efficacy and safety of belimumab, in combination with azathioprine, for the maintenance of remission following a standard induction regimen in patients with Wegener's granulomatosis or microscopic polyangiitis. The random assignment in this study is "1 to 1" which means that participants have an equal chance of receiving belimumab or placebo.

    View full details

  • A Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis (FSGS) Recruiting

    The primary objectives of this trial are as follows: - to compare the achievement of a partial remission (PR) or complete remission (CR) in urinary protein: creatinine ratio (Up/c ratio) in patients treated with fresolimumab versus placebo - to compare the safety profile of patients treated with fresolimumab versus placebo The secondary objectives are as follows: - To compare the reduction in proteinuria in patients treated with fresolimumab versus placebo - To evaluate fresolimumab dose-dependent reduction in proteinuria - To compare the change in renal function (estimated glomerular filtration rate [eGFR]) in patients treated with fresolimumab versus placebo - To evaluate the multiple-dose pharmacokinetics of fresolimumab

    View full details

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • Renal function in normal and disordered pregnancy CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION Hussein, W., Lafayette, R. A. 2014; 23 (1): 46-53

    Abstract

    Renal dysfunction during pregnancy is a common and serious complication. Understanding normal physiology during pregnancy provides a context to further describe changes in pregnancy that lead to renal dysfunction and may provide clues to better management.Hormonal changes during pregnancy allow for increased blood flow to the kidneys and altered autoregulation such that glomerular filtration rate (GFR) increases significantly through reductions in net glomerular oncotic pressure and increased renal size. The mechanisms for maintenance of increased GFR change through the trimesters of pregnancy, continuing into the postpartum period. Important causes of pregnancy-specific renal dysfunction have been further studied, but much needs to be learned. Pre-eclampsia is due to abnormal placentation, with shifts in angiogenic proteins and the renin-angiotensin-aldosterone system leading to endothelial injury and clinical manifestations of hypertension and organ dysfunction. Other thrombotic microangiopathies occurring during pregnancy have been better defined as well, with new work focusing on the contribution of the complement system to these disorders.Advances have been made in understanding the physiology of the kidney in normal pregnancy. Diseases that affect the kidney during pregnancy alter this physiology in various ways that inform clinicians on pathogenesis and may lead to improved therapeutic approaches and better outcomes of pregnancy.

    View details for DOI 10.1097/01.mnh.0000436545.94132.52

    View details for Web of Science ID 000327996700007

    View details for PubMedID 24247824

  • Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis HEART RHYTHM Varr, B. C., Zarafshar, S., Coakley, T., Liedtke, M., Lafayette, R. A., Arai, S., Schrier, S. L., Witteles, R. M. 2014; 11 (1): 158-162

    View details for DOI 10.1016/j.hrthm.2013.10.026

    View details for Web of Science ID 000329119200027

    View details for PubMedID 24121001

  • Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hogan, J., Bomback, A. S., Mehta, K., Canetta, P. A., Rao, M. K., Appel, G. B., Radhakrishnan, J., Lafayette, R. A. 2013; 8 (12): 2072-2081

    Abstract

    Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States.Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform.Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean SD, 7031 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI.Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

    View details for DOI 10.2215/CJN.02840313

    View details for Web of Science ID 000327951100008

    View details for PubMedID 24009220

  • Lenalidomide, melphalan and dexamethasone in a population of patients with immunoglobulin light chain amyloidosis with high rates of advanced cardiac involvement. Haematologica Dinner, S., Witteles, W., Afghahi, A., Witteles, R., Arai, S., Lafayette, R., Schrier, S. L., Liedtke, M. 2013; 98 (10): 1593-1599

    Abstract

    Immunoglobulin light chain amyloidosis remains incurable despite recent therapeutic advances, and is particularly difficult to treat in patients with amyloid cardiomyopathy. Based on evidence of activity in multiple myeloma, we designed a pilot study of an oral regimen of lenalidomide in combination with dexamethasone and low dose melphalan in order to evaluate its safety and efficacy in patients with amyloidosis, including those with advanced cardiac involvement. Twenty-five patients were enrolled. Ninety-two percent of patients had cardiac involvement by amyloidosis, and 36% of patients met criteria for Mayo Clinic cardiac stage III disease. Patients received up to 9 cycles of treatment, consisting of lenalidomide 10 mg/day orally on days 1 - 21 (28 day cycle); melphalan 0.18mg/kg orally on days 1-4; and dexamethasone 40 mg orally on days 1, 8, 15, 22. High rates (33%) of cardiac arrhythmias and low rates of treatment completion (12.5%) were observed. Ten patients died during the study, all within the first several months of treatment due to acute cardiac events. The overall hematologic response rate was 58%, however organ responses were seen in only 8% of patients. Overall survival at one year was 58%. While we confirmed the hematologic response rates observed with similar regimens, front line treatment with melphalan, lenalidomide and dexamethasone was toxic, ineffective, and did not alter survival outcomes for patients with high risk cardiac disease. Our data highlight the importance of developing novel treatment approaches for amyloid cardiomyopathy. The trial was registered at www.clinicaltrials.gov (NCT00890552).

    View details for DOI 10.3324/haematol.2013.084574

    View details for PubMedID 23716538

  • Red blood cell transfusion use in patients with chronic kidney disease NEPHROLOGY DIALYSIS TRANSPLANTATION Gill, K. S., Muntner, P., Lafayette, R. A., Petersen, J., Fink, J. C., Gilbertson, D. T., Bradbury, B. D. 2013; 28 (6): 1504-1515

    Abstract

    BACKGROUND: There is limited data available on the use of red blood cell (RBC) transfusions in younger chronic kidney disease patients not on dialysis (CKD-ND), for whom the consequences of developing antibodies to foreign antigens (allosensitization) may be particularly relevant. METHODS: We used the Ingenix medical claims database, comprising data on ?40 million commercially insured US individuals, to identify annual (2002-08) cohorts of patients 18-64 years of age with newly diagnosed CKD. We followed each cohort for 1 year to estimate RBC transfusion rates and used Cox proportional hazards regression to identify patient characteristics associated with time to first transfusion. RESULTS: We identified 120 790 newly diagnosed CKD patients for the years 2002-08; 54% were 50-64 years of age. Overall, the transfusion rate was 2.64/100 person-years (PYs) (95% CI: 2.52-2.77). Rates were higher among those with diagnosed anemia [9.80/100 PYs (95% CI: 9.31-10.3)] and among those who progressed to end-stage renal disease (ESRD) [28.0/100 PYs (95% CI: 23.7-33.0)]. For those progressing to ESRD, transfusion rates more than doubled between 2002 and 2008. Of the factors evaluated, transfusion history and the presence of heart failure and diabetes were most strongly associated with a receipt of a transfusion. CONCLUSIONS: RBC transfusions are relatively common and on the rise among younger CKD-ND patients who are anemic and progress to ESRD. Efforts to decrease the use of transfusions may be important for potential transplant candidates who progress to ESRD.

    View details for DOI 10.1093/ndt/gfs580

    View details for Web of Science ID 000321057700031

    View details for PubMedID 23389999

  • Renal Physiology of Pregnancy ADVANCES IN CHRONIC KIDNEY DISEASE Cheung, K. L., Lafayette, R. A. 2013; 20 (3): 209-214

    Abstract

    Pregnancy involves remarkable orchestration of physiologic changes. The kidneys are central players in the evolving hormonal milieu of pregnancy, responding and contributing to the changes in the environment for the pregnant woman and fetus. The functional impact of pregnancy on kidney physiology is widespread, involving practically all aspects of kidney function. The glomerular filtration rate increases 50% with subsequent decrease in serum creatinine, urea, and uric acid values. The threshold for thirst and antidiuretic hormone secretion are depressed, resulting in lower osmolality and serum sodium levels. Blood pressure drops approximately 10 mmHg by the second trimester despite a gain in intravascular volume of 30% to 50%. The drop in systemic vascular resistance is multifactorial, attributed in part to insensitivity to vasoactive hormones, and leads to activation of the renin-aldosterone-angiostensin system. A rise in serum aldosterone results in a net gain of approximately 1000 mg of sodium. A parallel rise in progesterone protects the pregnant woman from hypokalemia. The kidneys increase in length and volume, and physiologic hydronephrosis occurs in up to 80% of women. This review will provide an understanding of these important changes in kidney physiology during pregnancy, which is fundamental in caring for the pregnant patient.

    View details for DOI 10.1053/j.ackd.2013.01.012

    View details for Web of Science ID 000318464100003

    View details for PubMedID 23928384

  • The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis BRITISH JOURNAL OF HAEMATOLOGY Dinner, S., Witteles, W., Witteles, R., Lam, A., Arai, S., Lafayette, R., George, T. I., Schrier, S. L., Liedtke, M. 2013; 161 (3): 367-372

    Abstract

    The prevalence and prognostic value of a concomitant diagnosis of symptomatic or asymptomatic multiple myeloma (MM), as defined by the current International Myeloma Working Group (IMWG) criteria, in patients with immunoglobulin light chain amyloidosis (AL), are unknown. We studied 46 consecutive patients with AL who underwent quantification of serum M-protein and clonal bone marrow plasma cells, as well as a comprehensive evaluation for end organ damage by MM. Using standard morphology and CD138 immunohistochemical staining, 57% and 80% of patients were found to have concomitant MM, respectively. Nine patients exhibited end organ damage consistent with a diagnosis of symptomatic MM. While overall survival was similar between AL patients with or without concurrent myeloma (1-year overall survival 68% vs. 87%; P = 0.27), a diagnosis of symptomatic myeloma was associated with inferior outcome (1-year overall survival 39% vs. 81%; P = 0.005). Quantification of bone marrow plasma cells by both standard morphology and CD138 immunohistochemistry identified a much higher prevalence of concurrent MM in patients with AL than previously reported. Evaluation of bone marrow plasma cell infiltration and presence of myeloma associated end organ damage could be clinically useful for prognostication of patients with AL.

    View details for DOI 10.1111/bjh.12269

    View details for Web of Science ID 000317602300009

    View details for PubMedID 23432783

  • More Than a Frog in the Throat A Case Series and Review of Localized Laryngeal Amyloidosis ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Stevenson, R., Witteles, R., Damrose, E., Arai, S., Lafayette, R. A., Schrier, S., Afghahi, A., Liedtke, M. 2012; 138 (5): 509-511

    View details for Web of Science ID 000305415100012

    View details for PubMedID 22652951

  • Heart transplantation and cardiac amyloidosis: Approach to screening and novel management strategies JOURNAL OF HEART AND LUNG TRANSPLANTATION Varr, B. C., Liedtke, M., Arai, S., Lafayette, R. A., Schrier, S. L., Witteles, R. M. 2012; 31 (3): 325-331

    Abstract

    Limited data exist regarding screening methods and outcomes for orthotopic heart transplantation (OHT) in cardiac amyloidosis. As a result, uncertainty exists over the best approach to OHT for cardiac amyloidosis and for the timing of critical post-transplant therapies. This article reviews 6 patients who underwent OHT for cardiac amyloidosis at the Stanford University Amyloid Center from 2008 to present. All patients with light-chain amyloidosis received chemotherapy in the interval between OHT and autologous hematopoietic stem cell transplant. Five patients remain alive up to 25 months after OHT, without evidence of recurrent cardiac amyloid deposition. A novel strategy of OHT, followed by light-chain suppressive chemotherapy before autologous hematopoietic stem cell transplant, is feasible for patients with light-chain amyloidosis.

    View details for DOI 10.1016/j.healun.2011.09.010

    View details for Web of Science ID 000300806500015

    View details for PubMedID 22051505

  • Profiling of Autoantibodies in IgA Nephropathy, an Integrative Antibiomics Approach CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Sigdel, T. K., Woo, S. H., Dai, H., Khatri, P., Li, L., Myers, B., Sarwal, M. M., Lafayette, R. A. 2011; 6 (12): 2775-2784

    Abstract

    IgG commonly co-exists with IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) with unclear clinical relevance. Autoantibody (autoAb) biomarkers to detect and track progression of IgAN are an unmet clinical need. The objective of the study was to identify IgA-specific autoAbs specific to IgAN.High-density protein microarrays were evaluated IgG autoAbs in the serum of IgAN patients (n = 22) and controls (n = 10). Clinical parameters, including annual GFR and urine protein measurements, were collected on all patients over 5 years. Bioinformatic data analysis was performed to select targets for further validation by immunohistochemistry (IHC).One hundred seventeen (1.4%) specific antibodies were increased in IgAN. Among the most significant were the autoAb to the Ig family of proteins. IgAN-specific autoAbs (approximately 50%) were mounted against proteins predominantly expressed in glomeruli and tubules, and selected candidates were verified by IHC. Receiver operating characteristic analysis of our study demonstrated that IgG autoAb levels (matriline 2, ubiquitin-conjugating enzyme E2W, DEAD box protein, and protein kinase D1) might be used in combination with 24-hour proteinuria to improve prediction of the progression of IgAN (area under the curve = 0.86, P = 0.02).IgAN is associated with elevated IgG autoAbs to multiple proteins in the kidney. This first analysis of the repertoire of autoAbs in IgAN identifies novel, immunogenic protein targets that are highly expressed in the kidney glomerulus and tubules that may bear relevance in the pathogenesis and progression of IgAN.

    View details for DOI 10.2215/CJN.04600511

    View details for Web of Science ID 000297948900009

    View details for PubMedID 22157707

  • Serum relaxin levels and kidney function in late pregnancy with or without preeclampsia CLINICAL NEPHROLOGY Lafayette, R. A., Hladunewich, M. A., Derby, G., Blouch, K., Druzin, M. L., Myers, B. D. 2011; 75 (3): 226-232

    Abstract

    Relaxin, a potent pregnancy-related hormone, has been proposed to be a major mediator of renal physiology in normal pregnancy. We wished to test relaxin levels in pregnancy and preeclampsia.We performed precise physiologic measurements of kidney function in 38 normal peripartum women and 58 women with preeclampsia. We measured serum relaxin levels prior to delivery and over the first 4 postpartum weeks utilizing a modern, validated ELISA. Results were compared to those of 18 normal women of childbearing age.Relaxin levels were substantially elevated in women prior to delivery (364 268 vs. 15 16 pg/ml) and fell rapidly over the first postpartum week reaching normal non pregnant levels by Week 2 (32 64 vs. 15 16 pg/ml). No differences were seen between relaxin levels in normal pregnancy as compared to preeclampsia (364 268 vs. 376 241 pg/ml) despite substantial and persistent abnormalities in GFR (149 33 vs. 89 25 ml/min), albuminuria (14 vs. 687 mg/g) and mean arterial pressure (80 8 vs. 111 18). Furthermore no correlation could be established between physiologic measures (GFR, MAP, RBF, RVR) and relaxin levels (p > 0.3), either in the overall population or any of the subgroups.Relaxin is indeed significantly elevated in the serum of women during late pregnancy and the early puerperium. However, serum relaxin does not appear to influence BP, renal vascular resistance, renal blood flow or GFR in late pregnancy or in women with preeclampsia.

    View details for DOI 10.5414/CNP75226

    View details for Web of Science ID 000288817800007

    View details for PubMedID 21329633

  • Hemoglobinuria and Acute Kidney Injury Requiring Hemodialysis Following Intravenous Immunoglobulin Infusion AMERICAN JOURNAL OF KIDNEY DISEASES Welles, C. C., Tambra, S., Lafayette, R. A. 2010; 55 (1): 148-151

    Abstract

    Intravenous immunoglobulin (IVIG), a product initially developed for patients with immunodeficiencies, now has multiple other indications and increasing off-label use. IVIG generally is well tolerated, with few adverse effects. Antibody-mediated (Coombs-positive) hemolysis is known to occur after IVIG infusion, but often is subclinical and previously has not been reported to lead to acute kidney injury (AKI). The predominantly known mechanism of AKI after IVIG infusion has been osmotic nephrosis, primarily associated with sucrose-containing formulations. We present a case of a bone marrow transplant recipient who was treated with a sucrose-free IVIG product and subsequently developed Coombs-positive hemolysis leading to AKI requiring hemodialysis, who ultimately died secondary to infectious complications. The severity of this case emphasizes the importance of identifying populations who may be at increased risk of pigment-mediated kidney injury before consideration of IVIG therapy.

    View details for DOI 10.1053/j.ajkd.2009.06.013

    View details for Web of Science ID 000273958000020

    View details for PubMedID 19628320

  • Protocol adherence and the ability to achieve target haemoglobin levels in haemodialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Chan, K., Moran, J., Hlatky, M., Lafayette, R. 2009; 24 (6): 1956-1962

    Abstract

    Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels.A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl.Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation.Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

    View details for DOI 10.1093/ndt/gfn780

    View details for Web of Science ID 000266355500040

    View details for PubMedID 19176685

  • Imatinib in the Treatment of Nephrogenic Systemic Fibrosis AMERICAN JOURNAL OF KIDNEY DISEASES Chandran, S., Petersen, J., Jacobs, C., Forentino, D., Doeden, K., Lafayette, R. A. 2009; 53 (1): 129-132

    Abstract

    Nephrogenic systemic fibrosis is a disabling progressive condition that is being reported with increased frequency in patients with kidney disease. Treatment is extremely limited and largely supportive. We report a case of severe nephrogenic systemic fibrosis in a dialysis patient exposed to multiple doses of gadolinium who improved clinically and histologically with treatment with imatinib.

    View details for DOI 10.1053/j.ajkd.2008.08.029

    View details for Web of Science ID 000262172200018

    View details for PubMedID 19012999

  • Facility factors dominate the ability to achieve target haemoglobin levels in haemodialysis patients NEPHROLOGY DIALYSIS TRANSPLANTATION Chan, K. E., Lafayette, R. A., Whittemore, A. S., Hlatky, M. A., Moran, J. 2008; 23 (9): 2948-2956

    Abstract

    Our objective was to determine whether patient factors, processes of care and measures of erythropoietin (EPO) responsiveness were associated with successful anemia management at the individual patient level.We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0-12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility.Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26-2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58-3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = -0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility.The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients' EPO responsiveness, which may be influenced by facility care patterns.

    View details for DOI 10.1093/ndt/gfn172

    View details for Web of Science ID 000259372400039

    View details for PubMedID 18469314

  • Course of preeclamptic glomerular injury after delivery AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hladunewich, M. A., Myers, B. D., Derby, G. C., Blouch, K. L., Druzin, M. L., Deen, W. M., Naimark, D. M., Lafayette, R. A. 2008; 294 (3): F614-F620

    Abstract

    We evaluated the early postpartum recovery of glomerular function over 4 wk in 57 women with preeclampsia. We used physiological techniques to measure glomerular filtration rate (GFR), renal plasma flow, and oncotic pressure (pi(A)) and computed a value for the two-kidney ultrafiltration coefficient (K(f)). Compared with healthy, postpartum controls, GFR was depressed by 40% on postpartum day 1, but by only 19% and 8% in the second and fourth postpartum weeks, respectively. Hypofiltration was attributable solely to depression, at corresponding postpartum times, of K(f) by 55%, 30%, and 18%, respectively. Improvement in glomerular filtration capacity was accompanied by recovery of hypertension to near-normal levels and significant improvement in albuminuria. We conclude that the functional manifestations of the glomerular endothelial injury of preeclampsia largely resolve within the first postpartum month.

    View details for DOI 10.1152/ajprenal.00470.2007

    View details for Web of Science ID 000253574500019

    View details for PubMedID 18199600

  • Prediction of early progression in recently diagnosed IgA nephropathy NEPHROLOGY DIALYSIS TRANSPLANTATION Lemley, K. V., Lafayette, R. A., Derby, G., Blouch, K. L., Anderson, L., Efron, B., Myers, B. D. 2008; 23 (1): 213-222

    Abstract

    Most studies of prognosis in IgA nephropathy (IgAN) have tried to predict dichotomous outcomes based on a small number of clinical or semi-quantitative histological variables in large numbers of patients.We pursued a quite different approach. We measured GFR annually for 4-5 years in 22 adult patients with recently diagnosed IgAN. Quantitative morphology was performed on the diagnostic biopsy specimens and baseline glomerular filtration dynamics were performed at study entry. An initial set of 30 plausible predictor variables (half demographic or physiological, half structural) was reduced to 22 using phylogenetic trees. Least-angle regression (LARS) was used to predict the rate of GFR change from these variablesThe rate of GFR change ranged from a loss of 41 ml/min/year to a gain of 8.6 ml/min/year. We found an optimum predictor set of five baseline variables: the percentage of glomeruli with global sclerosis, the fractional interstitial area, the serum creatinine, the average tuft volume of non-sclerotic glomeruli and the renal plasma flow.The strong predictive relationship of the three structural variables with the slope of GFR in our subjects suggests that even at the time of their initial diagnosis many patients with IgAN already manifest a 'remnant kidney' phenomenon. The distinctive pathophysiological insights derived from this study suggest some of the advantages of intense quantitative investigations applied to a small number of subjects.

    View details for DOI 10.1093/ndt/gfm560

    View details for Web of Science ID 000253022100034

    View details for PubMedID 17890749

  • Pathophysiology of the clinical manifestations of preeclampsia CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hladunewich, M., Karumanchi, S. A., Lafayette, R. 2007; 2 (3): 543-549

    View details for DOI 10.2215/CJN.03761106

    View details for Web of Science ID 000246049100021

    View details for PubMedID 17699462

  • Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial. Obstetrics and gynecology Hladunewich, M. A., Derby, G. C., Lafayette, R. A., Blouch, K. L., Druzin, M. L., Myers, B. D. 2006; 107 (4): 886-895

    Abstract

    To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia.Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups.No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria.Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery.I.

    View details for PubMedID 16582128

  • Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients. Clinical and experimental nephrology Lentine, K. L., Parsonnet, J., Taylor, I., Wrone, E. M., Lafayette, R. A. 2006; 10 (1): 55-62

    Abstract

    Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients.We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01.Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome.Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.

    View details for PubMedID 16544178

  • Renal tubular injury associated with anagrelide NEPHROLOGY DIALYSIS TRANSPLANTATION Rodwell, G. E., Troxell, M. L., Lafayette, R. A. 2005; 20 (5): 988-990

    View details for DOI 10.1093/ndt/gfh726

    View details for Web of Science ID 000229083800022

    View details for PubMedID 15728271

  • The kidney in preeclampsia KIDNEY INTERNATIONAL Lafayette, R. 2005; 67 (3): 1194-1203

    View details for Web of Science ID 000227013500049

    View details for PubMedID 15698468

  • Examining chronic kidney disease management in a single center CLINICAL NEPHROLOGY Lafayette, R. A., Lai, G. 2004; 62 (4): 260-266

    Abstract

    The management of patients with chronic kidney disease in outpatient clinics was assessed for the ability to achieve targets of care advocated in clinical practice guidelines.272 records of outpatients with increased serum creatinine (> or = 1.5 mg/dl for women, > or = 2.0 mg/dl for men) were reviewed for details of their assessment and management. Prevailing data on blood pressure, anemia, bone disease and lipid status as well as therapeutic changes were evaluated.The subjects were aged 64 +/- 18 years, serum creatinine 2.6 +/- 1.1 mg/dl, and calculated GFR (MDRD formula) 19.2 +/- 9.9 ml/min. Median UproV was 1.0 (0.024 - 12.4) g/day. Causes of CKD were diabetes (33.5%), HTN (8.8%), GN (19.5%), and adult PKD (3.3%). Treatment targets were BP < 130/85 mmHg, Hct > or = 36%, serum Ca++ > or = 8.5 mg/dl, serum Po4 < 4.5 mg/dl and cholesterol < 200 mg/dl. Of the patients with abnormal findings, mean values for SBP were 153 +/- 17 mmHg, DBP 93 +/- 6 mmHg, Hct 31.7 +/- 2.9%, Ca++ 8.0 +/- 0.7 mg/dl, PO4 5.6 +/- 1.0 mg/dl, and cholesterol 236 +/- 37 mg/dl. Only a minority of patients with abnormal values had their treatment altered. Furthermore, only 54% of patients with hypertension were treated with either ACEi or ARB therapy. Finally, only 6% of patients with hypercholesterolemia had fasting lipid levels measured.This data suggests that treatment of patients with CKD has improved, but that many opportunities exist to optimize their care.

    View details for Web of Science ID 000224247300002

    View details for PubMedID 15524055

  • The dynamics of glomerular filtration in the puerperium AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hladunewich, M. A., Lafayette, R. A., Derby, G. C., Blouch, K. L., Bialek, J. W., Druzin, M. L., Deen, W. M., Myers, B. D. 2004; 286 (3): F496-F503

    Abstract

    We evaluated the glomerular filtration rate (GFR) during the second postpartum week in 22 healthy women who had completed an uncomplicated pregnancy. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). We compared these findings with those in pregnant women previously studied on the first postpartum day as well as nongravid women of reproductive age. Healthy female transplant donors of reproductive age permitted the morphometric analysis of glomeruli and computation of the single-nephron K(f). The aforementioned physiological and morphometric measurements were utilized to estimate transcapillary hydraulic pressure (Delta P) from a mathematical model of glomerular ultrafiltration. We conclude that postpartum day 1 is associated with marked glomerular hyperfiltration (+41%). A theoretical analysis of GFR determinants suggests that depression of glomerular capillary oncotic pressure, the force opposing the formation of filtrate, is the predominant determinant of early elevation of postpartum GFR. A reversal of the gestational hypervolemia and hemodilution, still evident on postpartum day 1, eventuates by postpartum week 2. An elevation of oncotic pressure in the plasma that flows axially along the glomerular capillaries to supernormal levels ensues; however, GFR remains modestly elevated (+20%) above nongravid levels. An analysis of filtration dynamics at this time suggests that a significant increase in Delta P by up to 16%, an approximately 50% increase in K(f), or a combination of smaller increments in both must be invoked to account for the persistent hyperfiltration.

    View details for DOI 10.1152/ajprenal.00194.2003

    View details for Web of Science ID 000188707500009

    View details for PubMedID 14612381

  • Podocytopenia and disease severity in IgA nephropathy KIDNEY INTERNATIONAL Lemley, K. V., Lafayette, R. A., Safai, M., Derby, G., Blouch, K., Squarer, A., Myers, B. D. 2002; 61 (4): 1475-1485

    Abstract

    IgA nephropathy is a common form of progressive glomerular disease, associated with proliferation of mesangial cells and mesangial deposition of IgA. The present study was designed to investigate functional and morphological covariates of disease severity in patients with IgA nephropathy.Glomerular hemodynamics, permselectivity and ultrastructure were studied in 17 adult patients with IgA nephropathy using inulin, para-aminohippuric acid (PAH) and 3H-Ficoll clearances and morphometric methods. A mathematical model of macromolecule permeation through a heteroporous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors and 12 healthy volunteers.The patients were heterogeneous in their disease severity, but as a group had a decreased glomerular filtration rate (GFR) and increased urinary protein excretion compared to controls [63 +/- 29 SD vs. 104 +/- 23 mL/min/1.73 m2, P < 0.001, and (median) 1.34 vs. 0.11 g/day, P < 0.0001, respectively). A multivariate analysis of structural and functional relationships revealed GFR depression to be most strongly correlated with the prevalence of global glomerular sclerosis (t = -4.073, P = 0.002). Those patients with the most severe glomerular dysfunction had a reduced number of glomerular visceral epithelial cells (podocytes) per glomerulus. The degree of podocytopenia was related to the extent of glomerular sclerosis and of impairment of permselectivity and GFR, with worsening injury below an apparent threshold podocyte number of about 250 cells per glomerulus. There were no corresponding correlations between these indices of injury and the number of mesangial and endothelial cells.Our findings show that podocyte loss is a concomitant of increasing disease severity in IgA nephropathy. This suggests that podocyte loss may either cause or contribute to the progressive proteinuria, glomerular sclerosis and filtration failure seen in this disorder.

    View details for Web of Science ID 000174465100030

    View details for PubMedID 11918755

  • How does knocking out angiotensin II activity reduce renal injury in mice? Discussion AMERICAN JOURNAL OF KIDNEY DISEASES Lafayette, R. A. 2000; 35 (1): 166-169

    View details for Web of Science ID 000084572400027

    View details for PubMedID 10620561

  • The dynamics of glomerular filtration after caesarean section JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lafayette, R. A., Malik, T., Druzin, M., Derby, G., Myers, B. D. 1999; 10 (7): 1561-1565

    Abstract

    The objective of this study was to determine whether the glomerular hyperfiltration of pregnancy is maintained even after Caesarean section and, if so, to define the responsible hemodynamics. The dynamics of glomerular filtration were evaluated in 12 healthy women who had just completed an uncomplicated pregnancy and were delivered by Caesarean section. Age-matched but non-gravid female volunteers (n = 22) served as control subjects. GFR in postpartum women was elevated above control values by 41%; 149+/-10 versus 106+/-3 ml/min per 1.73 m2, respectively (P < 0.001). In contrast, corresponding renal plasma flow was the same in the two groups, such that the postpartum filtration fraction was significantly elevated by 20%. Computation of glomerular intracapillary oncotic pressure (piGC) from knowledge of plasma oncotic pressure and the filtration fraction revealed this quantity to be significantly reduced in postpartum women, 20.6+/-1.7 versus 26.1+/-2.0 mmHg in control subjects (P < 0.001). A theoretical analysis of glomerular ultrafiltration suggests that depression of piGC, the force opposing the formation of filtrate, is predominantly or uniquely responsible for the observed postpartum hyperfiltration.

    View details for Web of Science ID 000081143900017

    View details for PubMedID 10405212

  • Nature of glomerular dysfunction in pre-eclampsia KIDNEY INTERNATIONAL Lafayette, R. A., Druzin, M., Sibley, R., Derby, G., Malik, T., Huie, P., Polhemus, C., Deen, W. M., Myers, B. D. 1998; 54 (4): 1240-1249

    Abstract

    Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia.Physiologic techniques were used to estimate glomerular filtration rate (GFR), renal plasma flow and afferent oncotic pressure immediately after delivery in consecutive patients with pre-eclampsia (PET; N = 13). Healthy mothers completing an uncomplicated pregnancy served as functional controls (N = 12). A morphometric analysis of glomeruli obtained by biopsy and mathematical modeling were used to estimate the glomerular ultrafiltration coefficient (Kf). Glomeruli from healthy female kidney transplant donors served as structural controls (N = 8).The GFR in PET was depressed below the control level, 91 +/- 23 versus 149 +/- 34 ml/min/1.73 m2, respectively (P < 0.0001). In contrast, renal plasma flow and oncotic pressure were similar in the two groups (P = NS). A reduction in the density and size of endothelial fenestrae and subendothelial accumulation of fibrinoid deposits lowered glomerular hydraulic permeability in PET compared to controls, 1.81 versus 2.58 x 10(-9) m/sec/PA. Mesangial cell interposition also curtailed effective filtration surface area. Together, these changes lowered the computed single nephron Kf in PET below control, 4.26 versus 6.78 nl/min x mm Hg, respectively.The proportionate (approximately 40%) depression of Kf for single nephrons and GFR suggests that hypofiltration in PET does not have a hemodynamic basis, but is a consequence of structural changes that lead to impairment of intrinsic glomerular ultrafiltration capacity.

    View details for Web of Science ID 000076096900022

    View details for PubMedID 9767540

  • Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chertow, G. M., Lazarus, J. M., Paganini, E. P., Allgren, R. L., Lafayette, R. A., Sayegh, M. H. 1998; 9 (4): 692-698

    Abstract

    To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

    View details for Web of Science ID 000072776600020

    View details for PubMedID 9555672

  • Renal artery stenosis in kidney transplants AMERICAN JOURNAL OF KIDNEY DISEASES Fervenza, F. C., Lafayette, R. A., Alfrey, E. J., Petersen, J. 1998; 31 (1): 142-148

    Abstract

    Transplant renal artery stenosis (TRAS) is an increasingly recognized complication of renal transplantation, with a reported incidence of between 1% and 23%. The clinical features include refractory hypertension, new-onset hypertension, allograft dysfunction, and the presence of a bruit over the graft. In this report, we describe the investigation and treatment of one such patient and review the current diagnostic approaches and therapy in this setting.

    View details for Web of Science ID 000071345700024

    View details for PubMedID 9428466

  • Pretransplant renal dysfunction predicts poorer outcome in liver transplantation CLINICAL NEPHROLOGY Lafayette, R. A., Pare, G., Schmid, C. H., King, A. J., Rohrer, R. J., Nasraway, S. A. 1997; 48 (3): 159-164

    Abstract

    The postoperative courses of 115 liver transplant recipients were reviewed to monitor for outcomes of acute renal failure and mortality. An analysis of baseline (preoperative) variables with particular attention to baseline renal function was accomplished to establish predictive variables for a complicated postoperative course. Acute renal failure requiring dialysis occurred in 27 cases (23%) and was associated with a prolonged ICU stay, greater infectious complications, greater hospital charges and a high mortality rate (46 +/- 11% vs. 9 +/- 3%) as compared to patients who did not experience acute renal failure. Death occurred in 20 patients (17%) overall prior to discharge. In order to assess the contribution of renal function, the population was divided arbitrarily into two groups based on preoperative serum creatinine. Group 1 (n = 50) had a preoperative serum creatinine < 1.0 mg/dl (mean +/- SD = 2.2 +/- 0.2 mg/dl) and Group 2 (n = 65) had a preoperative serum creatinine < or = 1.0 mg/dl (0.7 +/- 0.1 mg/dl). The groups experienced similar operative courses. Group 1 patients experienced significantly longer ICU stays (18 +/- 3 vs. 10 +/- 2 days), higher rates of acute renal failure requiring dialysis (52 +/- 7 vs. 5 +/- 2%), higher hospital charges (231,454 +/- 17,088 vs. 178,755 +/- 14,744 $, US) and a greatly increased mortality rate (32 +/- 1 vs. 6 +/- 1%), as compared to Group 2 patients. A multifactorial regression analysis demonstrated that of all pretransplant factors analyzed, elevation in the serum creatinine was significantly associated and was the strongest predictor of both outcomes: acute renal failure requiring dialysis (ROC = 0.89) and death (ROC = 0.83). The presence or absence of hepatorenal syndrome did not influence the results of this analysis. This study demonstrates that cirrhotic patients with renal dysfunction, as indicated by an elevated serum creatinine, experience a poor surgical outcome following liver transplantation. These patients may require special attention in the perioperative period. Alternatively, these data may influence the selection of ideal candidates for liver transplantation, where scarce resources need to be applied appropriately.

    View details for Web of Science ID A1997XV89900005

    View details for PubMedID 9342487

  • Profound hypophosphatemia and isolated hyperphosphaturia in two cases of multiple myeloma AMERICAN JOURNAL OF KIDNEY DISEASES Dash, T., Parker, M. G., Lafayette, R. A. 1997; 29 (3): 445-448

    Abstract

    We describe the development of severe hypophosphatemia and urinary phosphate wasting in two patients with multiple myeloma. In both cases, the serum phosphorus was repeatedly less than 1.0 mg/dL despite vigorous replacement, and the calculated fractional excretion of urinary phosphorus was greater than 100%. Neither patient demonstrated other tubular defects typical of Fanconi's syndrome. With treatment of the myeloma, both patients achieved normalization of the serum phosphorus and no longer required phosphorus supplementation. We believe that multiple myeloma should be considered in the differential diagnosis in patients with profound hypophosphatemia, urinary phosphate wasting, and otherwise intact tubular function.

    View details for Web of Science ID A1997WK38800016

    View details for PubMedID 9041222

  • Acute renal failure due to postinfectious glomerulonephritis during pregnancy AMERICAN JOURNAL OF KIDNEY DISEASES Fervenza, F., Green, A., Lafayette, R. A. 1997; 29 (2): 273-276

    Abstract

    Acute renal failure is a rare but potentially devastating complication of pregnancy. Among its many potential causes is acute postinfectious glomerulonephritis. We describe a case of acute renal failure during pregnancy, provide the histologic features of the renal biopsy, and discuss the differential diagnosis. Postinfectious glomerulonephritis can present rapidly after clinical infection and cause acute renal failure in pregnancy.

    View details for Web of Science ID A1997WH36400014

    View details for PubMedID 9016900

  • PREVENTING DISEASE PROGRESSION IN CHRONIC-RENAL-FAILURE AMERICAN FAMILY PHYSICIAN Lafayette, R. A. 1995; 52 (6): 1783-1791

    Abstract

    Progression toward end-stage renal disease is usually inexorable in patients with diabetic and nondiabetic nephropathy. These patients can be identified at an early stage based on history, abnormal urinalysis or reduced glomerular filtration. Recent advances have made it possible to slow the progression of chronic renal failure. Major interventions include antihypertensive therapy, dietary protein restriction and, in patients with diabetes, strict glycemic control and angiotensin-converting enzyme inhibitor therapy. Collaboration with a nephrologist can help guide the family physician in the appropriate use of these modalities and help avoid common complications. Major efforts in slowing the progression of renal failure may lead to a decreased incidence of end-stage renal disease, with savings in morbidity, mortality and cost.

    View details for Web of Science ID A1995TC86900021

    View details for PubMedID 7484688

  • INCREASED SERUM CREATININE IN THE ABSENCE OF RENAL-FAILURE IN PROFOUND HYPOTHYROIDISM AMERICAN JOURNAL OF MEDICINE Lafayette, R. A., Costa, M. E., King, A. J. 1994; 96 (3): 298-299

    View details for Web of Science ID A1994ND10900019

    View details for PubMedID 8154519

  • THE EFFECTS OF BLOOD-PRESSURE REDUCTION ON CYCLOSPORINE NEPHROTOXICITY IN THE RAT JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lafayette, R. A., Mayer, G., Meyer, T. W. 1993; 3 (12): 1892-1899

    Abstract

    The effects of blood pressure reduction on cyclosporine nephrotoxicity were studied over 12 months in four groups of rats. Group 1 received no drugs and served as controls. Groups 2, 3, and 4 received cyclosporine (CyA), approximately 9 mg/kg.day, in their food. In addition, Group 3 received enalapril and Group 4 received minoxidil, hydrochlorothiazide, and reserpine. Time-averaged monthly systolic blood pressure was equal in Groups 1 and 2 (136 +/- 1 and 135 +/- 1 mm Hg, respectively). Antihypertensive agents reduced average systolic blood pressure in Groups 3 and 4 (116 +/- 1 and 117 +/- 1 mm Hg, respectively). Morphometric studies showed that 12 months of CyA treatment caused interstitial fibrosis with an increase in the fractional volume of cortical interstitium (VvInt: Group 2, 20 +/- 1%; Group 1, 11 +/- 1%) and a reduction in mean glomerular volume (VG. Group 2, (2.00 +/- 0.06) x 10(6) mu 3; Group 1, (2.48 +/- 0.06) x 10(6) mu 3). These structural changes were accompanied by a significant reduction in GFR (Group 2, 2.27 +/- 0.10 mL/min; Group 1, 2.76 +/- 0.10 mL/min). Cotreatment with enalapril reduced interstitial fibrosis (VvInt, 14 +/- 1%) and maintained VG (2.23 +/- 0.08 x 10(6) mu 3) and GFR (2.56 +/- 0.08 mL/min) at near-normal values in Group 3. In contrast, the combination antihypertensive regimen increased the extent of interstitial fibrosis (VvInt, 24 +/- 1%) and further lowered VG (1.72 +/- 0.05 x 10(6) mu 3) and GFR (1.72 +/- 0.05 mL/min) in Group 4. These results show that sustained treatment with a moderate dose of CyA causes interstitial fibrosis and impairs renal function in rats. The administration of enalapril, but not minoxidil, reserpine, and hydrochlorothiazide, limits renal injury in this model.

    View details for Web of Science ID A1993LJ29800007

    View details for PubMedID 8338921

  • EFFECTS OF ANGIOTENSIN-II RECEPTOR BLOCKADE ON REMNANT GLOMERULAR PERMSELECTIVITY KIDNEY INTERNATIONAL Mayer, G., Lafayette, R. A., Oliver, J., Deen, W. M., Myers, B. D., Meyer, T. W. 1993; 43 (2): 346-353

    Abstract

    This study examined the mechanisms by which angiotensin II (Ang II) receptor blockade improves glomerular barrier function in rats with reduced nephron number. Proteinuria was measured at four weeks after 5/6 renal ablation, and rats were then divided into a group which received the Ang II receptor blocker MK954 and a group which received no treatment. Studies performed one week later showed that Ang II receptor blockade reduced proteinuria without altering GFR in renal ablated rats. Micropuncture studies showed that Ang II blockade reduced both mean arterial pressure (142 +/- 7 mm Hg, ablation without treatment; 105 +/- 2 mm Hg, ablation with treatment) and glomerular transcapillary pressure (54 +/- 3 mm Hg, ablation without treatment; 43 +/- 1 mm Hg, ablation with treatment). Dextran sieving studies showed that untreated rats developed a size-selective defect characterized by increased transglomerular passage of neutral dextrans with radii 54 to 76 A and a charge-selective defect characterized by an increased transglomerular passage of anionic dextran sulfate with a radius of approximately 18 A. Ang II blockade reduced fractional clearance values for large neutral dextrans near to values observed in normal rats but had no effect on the fractional clearance of dextran sulfate (0.68 +/- 0.11, ablation without treatment; 0.66 +/- 0.08, ablation with treatment; 0.46 +/- 0.05, normal rats). These findings indicate that reducing Ang II activity improves size-selectivity without affecting charge-selectivity in injured remnant glomeruli.

    View details for Web of Science ID A1993KH90700009

    View details for PubMedID 7680077

  • ANGIOTENSIN-II RECEPTOR BLOCKADE LIMITS GLOMERULAR INJURY IN RATS WITH REDUCED RENAL MASS JOURNAL OF CLINICAL INVESTIGATION Lafayette, R. A., Mayer, G., Park, S. K., Meyer, T. W. 1992; 90 (3): 766-771

    Abstract

    The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/- 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure.

    View details for Web of Science ID A1992JN95900012

    View details for PubMedID 1522231

Conference Proceedings


  • Anaritide in acute tubular necrosis Allgren, R. L., Marbury, T. C., Rahman, S. N., Weisberg, L. S., Fenves, A. Z., Lafayette, R. A., Sweet, R. M., Genter, F. C., Kurnik, B. R., Conger, J. D., Sayegh, M. H. MASS MEDICAL SOC. 1997: 828-834

    Abstract

    Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide.We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis. The patients received a 24-hour intravenous infusion of either anaritide (0.2 microgram per kilogram of body weight per minute) or placebo. The primary end point was dialysis-free survival for 21 days after treatment. Other end points included the need for dialysis, changes in the serum creatinine concentration, and mortality.The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group (P = 0.35). In the prospectively defined subgroup of 120 patients with oliguria (urinary output, < 400 ml per day), dialysis-free survival was 8 percent in the placebo group (5 of 60 patients) and 27 percent in the anaritide group (16 of 60 patients, P = 0.008). Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most. Conversely, among the 378 patients without oliguria, dialysis-free survival was 59 percent in the placebo group (116 of 195 patients) and 48 percent in the anaritide group (88 of 183 patients, P = 0.03).The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis.

    View details for Web of Science ID A1997WN37100003

    View details for PubMedID 9062091

Footer Links:

Stanford Medicine Resources: