A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome

Ponticelli, Claudio; Rizzoni, Gianfranco; Edefonti, Alberto; Altieri, Paolo; Rivolta, E.; Rinaldi, Stefano; Ghio, Luciana; Lusvarghi, E; Gusmano, Rosanna; Locatelli, Francesco; Pasquali, Sonia; Castellani, A; Della, Ornella; Casa-Alberighi,

doi:10.1007/bf00858129

Cited by 41 publications

(69 citation statements)

References 7 publications

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“…Although cyclosporine seems to achieve a more rapid remission than cyclophosphamide, between 60 and 90% of patients relapse after the medication is discontinued, making cyclosporine dependence a major problem (23). Furthermore, both cyclosporine and cyclophosphamide have significant adverse effects with prolonged and recurrent use.…”

Section: Discussionmentioning

confidence: 99%

Adult Minimal-Change Disease

Waldman

Crew²,

Valeri³

et al. 2007

Clinical Journal of the American Society of Nephrology

361

439

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Minimal-change disease (MCD) counts for 10 to 15% of cases of primary nephrotic syndrome in adults. Few series have examined this disease in adults. A retrospective review was performed of 95 adults who had MCD and were seen at a single referral center. Examined were presenting features, response to daily versus alternate-day steroids, response to second-line agents, relapse patterns, complications of the disease and therapy, presence of acute renal failure (ARF), and outcome data. Sixty-five patients received daily and 23 received alternate-day steroids initially. There were no differences in remissions, time to remission, relapse rate, or time to relapse between daily-and alternate-day-treated patients. More than one quarter of patients were steroid resistant. At least one relapse occurred in 73% of patients; 28% were frequently relapsing. A significant proportion of frequently relapsing patients became steroid dependent. Second-line agents were used for steroid dependence, steroid resistance, or frequent relapses. No single agent proved superior. There were more remissions with second-line agents in steroid-dependent patients compared with steroid-resistant patients, and remissions were more likely to be complete in steroid-dependent patients. ARF occurred in 24 patients; they tended to be older and hypertensive with lower serum albumin and more proteinuria than those without ARF. At follow up, patients with an episode of ARF had higher serum creatinine than those without ARF. Four patients progressed to ESRD. These patients were less likely to have responded to steroids and more likely to have FSGS on repeat renal biopsy. In this referral MCD population, response to daily and alternate-day steroids is similar. Second-line agents give greater response in patients who are steroid dependent. ARF occurs in a significant number of adult MCD patients and may leave residual renal dysfunction. Few patients progress to ESRD. M inimal-change disease (MCD) is the most common cause of the nephrotic syndrome (NS) in children. It accounts for 70 to 90% of the NS in children who are younger than 10 yr and 50% in older children. It is also an important cause of primary NS in adults of all ages, accounting for 10 to 15% of cases (1,2). Although there are many data regarding the course, response to treatment, and outcomes in pediatric patients, only a few series have examined these issues in adults (3-8). Relatively less is known about the presentation of MCD in adult patients, response to agents other than steroids, the risk for acute renal failure (ARF), and the long-term outcome. Moreover, most series of adults with MCD have not been in US populations, and it is unknown whether the features and course of the disease are the same in differing parts of the world.We therefore performed a retrospective review of 95 patients who had primary adult-onset MCD and were treated at a single tertiary care center in the past 15 yr. Many of the patients were referred by outside nephrologists for opinions regarding treatment. This review...

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Section: Discussionmentioning

confidence: 99%

Adult Minimal-Change Disease

Waldman

Crew²,

Valeri³

et al. 2007

Clinical Journal of the American Society of Nephrology

361

439

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“…It is well established that immunological factors are involved in the development of GVHD such as: (1) donor T-lymphocyte cytokine release which may change glomerular permeability; and (2) minor disparities between donor and recipient MHC, responsible for the GVHD phenomenon as a whole. 8,9 The clear improvement of NS is due to CsA inhibition of interleukin and interferon gamma production by donor T-lymphocytes, which may be responsible for the glomerular permeability alterations in NS.…”

Section: Discussionmentioning

confidence: 99%

Nephrotic syndrome as a clinical manifestation of graft-versus-host disease (GVHD) in a marrow transplant recipient after cyclosporine withdrawal

Oliveira

Bahia

Franco

et al. 1998

Bone Marrow Transplant

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Summary:GVHD is one of the most frequent complications of BMT and recently nephrotic syndrome (NS) has been described as a manifestation of chronic GVHD. Here, we present an AA patient who developed NS 1 year after BMT when cyclosporine was stopped. Renal biopsy showed focal sclerosis associated with membranous deposits. He also had other clinical manifestations of chronic GVHD: sicca-like syndrome and colestasis. After 15 days of CsA therapy, he experienced a remarkable improvement in the NS and GVHD as a whole. We comment on immunological mechanisms that could be involved in the pathogenesis of this manifestation.

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“…However, the risk of clinical relapse can be as high as 85% at 5 years (8), requiring reiteration of prednisone courses, often with the additional use of calcineurin inhibitors, that is, cyclosporin A or tacrolimus (9,10). Long-term treatment with prednisone and calcineurin inhibitors increases the risk of complications such as neurotoxicity, renal failure, malignancy, growth retardation, hypertension, and diabetes.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome

Ravani

Magnasco

Edefonti

et al. 2011

Clinical Journal of the American Society of Nephrology

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188

148

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SummaryBackground and objectives Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission. Design, setting, participants, & measurementsThis open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m 2 intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome.Results Fifty-four children (mean age 11 Ϯ 4 years) with INS dependent on prednisone and calcineurin inhibitors for Ͼ12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P ϭ 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P Ͻ 0.001); 50% of RTX cases were in stable remission without drugs after 9 months.Conclusions Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal.

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A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome

Cited by 41 publications

References 7 publications

Adult Minimal-Change Disease

Adult Minimal-Change Disease

Nephrotic syndrome as a clinical manifestation of graft-versus-host disease (GVHD) in a marrow transplant recipient after cyclosporine withdrawal

Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome

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