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ABSTRACT: The number of kidneys obtained from deceased diabetic donors available for transplantation has increased >eightfold increase in the past 15 years. We assessed allograft outcomes associated with deceased diabetic donors and compared them with that of standard and extended criteria donors (ECD) in the UNOS data registry. We identified 1982 recipients of diabetic standard criteria donors over a 10-year period from 1995 through 2004. Both overall and death-censored survival of organs from diabetic standard criteria donors was significantly better than that of organs obtained from nondiabetic ECD while inferior to that from nondiabetic standard criteria donors. Compared with ECD donors, diabetic donors had lower serum creatinine, less cold ischemia and these kidneys were less likely to be pump-perfused. Recipients of diabetic kidneys were younger and less likely to experience delayed graft function compared with recipient of ECD kidneys. More recently, many diabetic donor kidneys have been given to diabetic recipients with early graft survival being similar to that among nondiabetic recipients. These findings demonstrate the potential to expand and to improve utilization of this resource without compromising outcomes for recipients. Improved, evidence-based evaluation and allocation of deceased diabetic donor kidneys is needed to optimize their use.
American Journal of Transplantation 07/2012; 12(8):2098-105. · 6.39 Impact Factor
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ABSTRACT: The induction therapy used in the management of Class III and IV lupus nephritis has been narrowed down to a choice between cyclophosphamide (CYC) and mycophenolate mofetil (MMF). However, there has been variability in the response to these agents, which may relate to demographic factors. In this study, we analyzed geographic factors affecting the response to CYC or MMF with a stratified meta-analysis.
We found and included 11 studies for our analyses--7 randomized controlled trials (RCTs) and 4 non-RCTs--that were stratified as being in Asia or elsewhere.
Meta-analysis of Asian studies showed no difference between regimens (RR = 0.98, 95% CI 0.74-1.28, p = ns) and no heterogeneity. The 2 RCT's from outside Asia showed significant advantage of MMF as induction therapy (RR = 3.69, 95%CI 1.45-9.3, p < 0.01) without heterogeneity. Together there was significant heterogeneity (Q = 11.69, I2 = 57.2%, p < 0.05) suggesting that the overall heterogeneity results from a difference between these groups. We repeated this analysis with the multicenter ALMS trial with their reported ethnicity-specific data. Again, no significant heterogeneity was seen in either subgroup (Asian: Q = 2.08, I2 = 0%, p = ns; Others: Q = 4.49, I2 = 55.5%, p = ns). Studies from Asia did not show a significant improvement with the use of MMF (RR = 1.06, 95%CI 0.79-1.41, p = ns) while data from RCTs conducted outside Asia suggested a greater likelihood of complete remission with the use of MMF (RR = 1.85, 95%CI 1.03-3.29, p < 0.05).
Our analysis demonstrates a higher likelihood of complete remission with MMF in patients outside Asia.
Clinical nephrology 03/2011; 75(3):233-41. · 1.17 Impact Factor
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ABSTRACT: FSGS is an important cause of ESRD and tends to recur in allografts (rFSGS). Older series suggest recurrence rates of 30-60%. In the modern era of transplant immunosuppression, recurrence rates are unknown. There are also few data regarding prevalence of known genetic mutations in adult FSGS patients who undergo transplantation. Recently, FSGS has been subdivided into histological variants, which may predict renal outcomes; there is little information on patterns of recurrence and outcomes in these variants. Finally, treatment for rFSGS relies upon up-titrating calcineurin inhibitors and plasmapheresis. Insufficient information exists on the use of these regimens for rFSGS in the era of modern immunosuppression. We conducted a retrospective chart review involving all renal transplant recipients at Columbia University Medical Center from December 1999 to March 2007. Those with biopsy confirmed primary FSGS were included and information regarding baseline characteristics, histologic variants, genetics, treatment, and clinical outcomes were collected. FSGS recurred in 23% of patients. Those with collapsing histology on native kidney biopsy, tended to recur with the same histology. No known genetic mutations were identified among those with recurrence. Plasmapheresis resulted in complete or partial remission in 75% of those with recurrence. Recurrent FSGS resulted in a trend toward the combined outcome of ESRD or death compared to those without recurrence (27% vs. 12%). Modern immunosuppression does not reduce the rate of rFSGS, known genetic mutations are uncommon in such adult patients, collapsing FSGS tends to recur with the same histology, and plasmapheresis may be helpful in the treatment of recurrence.
Clinical nephrology 09/2010; 74(3):173-81. · 1.17 Impact Factor
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Kidney International 05/2008; 74(6):817-21. · 6.61 Impact Factor
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ABSTRACT: Lupus nephritis (LN) in systemic lupus erythematosus (SLE) remains a major cause of morbidity and end-stage renal disease. While therapies such as corticosteroids, cyclophosphamide, and mycophenolate mofetil have improved outcomes, a significant proportion of patients have refractory disease or are unable to tolerate these agents. Limitations in existing therapies, along with advances in our understanding of the immunopathogenesis of SLE, have resulted in the development of new immunosuppressive and immunomodulatory treatments for SLE/LN. Dysfunction of the B lymphocyte-an important component of adaptive immunity-is thought to be important in the pathogenesis of SLE/LN. The goal of this study is to review our current understanding of the role of B cells in the pathogenesis of SLE, and to discuss new and emerging therapies that selectively target B cells in patients with SLE/LN. Novel strategies discussed include B-cell depletion by the monoclonal antibodies to B-cell markers, rituximab and epratuzumab; 'pharmapheresis' of pathogenic antibodies to dsDNA, by abetimus; blockade of T-cell costimulation of B cells by abatacept, belatacept, BG9588, and IDEC-131; and blockade of B-cell stimulation by belimumab. Preliminary results are promising, but in the absence of large controlled trials, caution must be exercised prior to the widespread use and acceptance of these treatments.
Kidney International 03/2008; 73(3):261-8. · 6.61 Impact Factor
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Kidney International 05/2007; 71(7):706-10. · 6.61 Impact Factor
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Kidney International 01/2007; 70(12):2152-5. · 6.61 Impact Factor
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ABSTRACT: The treatment of primary glomerular diseases has previously focused on relatively toxic immunosuppressive regimens. We are now seeing a paradigm shift from these toxic 'nonspecific' therapies to selective immunomodulating and immunosuppressive regimens. In this article, the experience with these newer agents including mycophenolate, rituximab, sirolimus, calcineurin inhibitors, and eculizumab are described.Keywords: glomerular disease, mycophenolate, rituximab, sirolimus, calcineurin inhibitors, eculizumab
Kidney International 11/2006; · 6.61 Impact Factor
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Kidney International 08/2006; 70(2):399-402. · 6.61 Impact Factor
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Kidney International 02/2006; 69(1):7. · 6.61 Impact Factor
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ABSTRACT: Acute renal failure (ARF) in hospitalized patients remains associated with significant morbidity and mortality. Most reports have detailed the in-hospital outcomes in ARF patients. This commentary focuses on the outcomes (including quality of life) of ARF patients, both adults and children, after discharge from the hospital.
Kidney International 02/2006; 69(1):17-9. · 6.61 Impact Factor
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ABSTRACT: Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high-dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.
Transplant Infectious Disease 07/2005; 7(2):75-9. · 2.22 Impact Factor
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ABSTRACT: The nephrotic syndrome occurs in association with a diverse array of primary and secondary glomerular disorders. Despite the different etiologies, many of the clinical effects are similar. This review focuses on the pathogenesis and treatment of edema formation, hyperlipidemia, and the hypercoagulable state. Major abnormalities of the endocrine system and evidence of erythropoietin deficiency will be reviewed. Finally, non-specific treatments aimed at reducing proteinuria will also be discussed.
Clinical nephrology 11/2004; 62(4):245-59. · 1.17 Impact Factor
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ABSTRACT: We report the clinical and pathologic findings in 7 patients with systemic lupus erythematosus and minimal change disease. All 7 patients presented with full nephrotic syndrome including peripheral edema, nephrotic range proteinuria (mean 9.6 g/day), and hypoalbuminemia (mean 1.8 g/dl). In all cases, renal biopsy revealed diffuse foot process effacement in the absence of significant peripheral capillary wall immune deposits, findings consistent with minimal-change disease. In addition, 5 cases displayed mesangial electron-dense deposits, with or without associated mesangial proliferation, consistent with underlying lupus nephritis class II. In all cases, steroid therapy induced a rapid remission of nephrotic syndrome. Minimal change disease is an underrecognized and readily reversible form of nephrotic syndrome in systemic lupus erythematosus. Because it may occur superimposed on mild mesangial proliferative lupus nephritis, this entity may be misinterpreted as an atypical presentation of lupus nephritis class II. Proper recognition of this entity requires careful integration of the renal biopsy immunofluorescence and electron microscopic findings.
Clinical nephrology 03/2002; 57(2):120-6. · 1.17 Impact Factor
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ABSTRACT: The influence of racial and socioeconomic factors on the incidence, prognosis, and response to therapy of many diseases has long been noted. Although glomerular diseases comprise 10% to over 16% of the dialysis and renal transplant populations, respectively, only recently have racial and socioeconomic factors been evaluated. Several glomerular diseases are associated with a striking African-American predominance. These include idiopathic focal sclerosis, and especially its collapsing variant, human immunodeficiency virus (HIV)-associated nephropathy, and severe lupus nephritis. In many of these entities the renal disease is also more aggressive and rapidly progressive than in other populations. Recent data points to genetic-biologic as well as social and economic factors that may be responsible for these findings. Studies dealing with the therapy of glomerular lesions must be stratified for racial and social background differences to avoid bias in outcome. Whether racial and socioeconomic data should be used in treating individual patients, and how, remains an area of controversy.
Seminars in Nephrology 08/2001; 21(4):403-10. · 2.12 Impact Factor
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ABSTRACT: The antiphospholipid syndrome is a disorder of hypercoagulability in association with circulating antiphospholipid antibodies directed against epitopes on oxidized phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Disorders associated with antiphospholipid antibodies but not the antiphospholipid syndrome, such as HIV and hepatitis C infection, appear to lack antibodies to beta 2-glycoprotein I. Patients with systemic lupus erythematosus have a high incidence of antiphospholipid antibodies with a high risk of thrombosis, often associated with anticardiolipin antibodies, beta 2-glyocoprotein I antibodies, and the presence of the lupus anticoagulant. Antiphospholipid antibodies are a significant cause of morbidity and mortality in renal patients with and without systemic lupus erythematosus. Renal manifestations include thrombotic microangiopathy and large vessel thrombosis. In patients with end-stage renal disease, antiphospholipid antibodies are prevalent and may increase in frequency with time on dialysis, possibly as a result of oxidative stress incurred during dialysis. The presence of anticardiolipin antibodies have been associated with a high incidence of hemodialysis access clotting. In renal transplant recipients, the incidence of antiphospholipid antibodies is also elevated and may be associated with a higher incidence of primary graft non-function. Although patients with systemic lupus erythematosus have similar renal allograft survival rates to the general population, survival is worse for those patients who are also antiphospholipid antibody positive. Additionally, in hepatitis C positive renal transplant recipients, the presence of anticardiolipin antibodies confers an increased risk of thrombotic complications and the development of thrombotic microangiopathy. Treatment of antiphospholipid antibody syndrome remains centered around anticoagulation with warfarin. The use of immunosuppressive agents has had no dramatic effect on antiphospholipid antibody titers and little clinical effect on thrombotic events.
Current Opinion in Nephrology and Hypertension 04/2001; 10(2):175-81. · 4.33 Impact Factor
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ABSTRACT: End-stage renal disease (ESRD) is associated with an overall one-year mortality of 23.5% in the US, of which cardiac causes constitute 50% of all deaths. Data on incident ESRD patients were obtained from the Health Care Financing Administration's 2728 and 2746 forms by special request from the ESRD Network of New York. 4,948 ESRD patients, who started dialysis in New York State from April 1, 1995, through April 1, 1996, were assessed to identify risk factors present at the initiation of dialysis that predict cardiac death. 899 deaths were registered during the 19-month-follow-up period, 50% of which were from cardiac causes. Using the Cox-proportional hazards model, the increasing age category, white race, the presence of one or more vascular co-morbid conditions, and the presence of diabetes and one or more cardiac co-morbid conditions significantly predicted cardiac death (p < 0.05). Diabetes increased the risk for cardiac death by 48% for those patients without any cardiac co-morbidities (RR = 1.48, p < 0.0082). In contrast with results observed in the general population, gender, serum albumin and body mass index were not significant predictors of cardiac death. In identifying risk factors present at the initiation ofdialysis that predict cardiac death, this study highlights factors that may be modified prior to dialysis initiation in order to improve life expectancy and mortality rates and decrease health care costs for the ESRD population.
Clinical nephrology 03/2001; 55(2):101-8. · 1.17 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic for the disease. Different forms of glomerulonephritis can occur in patients with SLE and can contribute significantly to the associated morbidity and, ultimately, mortality from the disease. Over the past two decades, there have been significant strides in our understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal damage and end-stage renal disease. In this chapter, we review the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discuss the experimental and human data regarding some of the potential newer forms of therapy. We discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD40 ligand, and CTLA4Ig.
Annual Review of Medicine 02/2001; 52:63-78. · 9.94 Impact Factor
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ABSTRACT: Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Optimal therapy for this disease is still debated. We report our experience using mycophenolate mofetil (MMF), an immunosuppressive agent widely used in transplant recipients, to treat 16 nephrotic patients with MN. All patients had biopsy-documented MN; secondary forms were ruled out. Fifteen patients had steroid-resistant disease; cytotoxic agents had failed in 6 patients and cyclosporine therapy had failed in 5 patients. Patients were treated with MMF (dose range, 500 to 2,000 mg) for a mean of 8 months. Six patients experienced a halving of proteinuria, which occurred after a mean duration of 6 months of therapy. Partial remissions occurred in 2 patients. There were no significant changes in mean values for serum creatinine, serum albumin, or proteinuria. Mean cholesterol levels were significantly less. Side effects of MMF were infrequent and generally mild. In summary, MMF appears to reduce proteinuria in some patients with idiopathic MN previously resistant to steroids, cytotoxic agents, or cyclosporine. Further trials with this agent are warranted.
American Journal of Kidney Diseases 09/2000; 36(2):250-6. · 5.43 Impact Factor
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ABSTRACT: This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
Journal of the American Society of Nephrology 09/2000; 11(8):1439-48. · 9.66 Impact Factor
