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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Rituximab Treatment for Adults with Refractory Nephrotic Syndrome: A Single-Center Experience and Review of the Literature

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          Abstract

          Background/Aims: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are common causes of nephrotic syndrome (NS) in adults. However, induction of remission and sustained control of proteinuria is often difficult. Recently, B cell-directed therapy using the anti-CD20 antibody rituximab has been suggested as induction regimen in pediatric FSGS and MCD patients. Data on rituximab use in adults are still limited. Methods: We report on rituximab use in five consecutively treated adult patients (mean age 42.2 ± 9.9 years) with FSGS or relapsing MCD (2 FSGS, 3 MCD) who failed to respond to standard immunosuppressive treatment. Median follow-up was 8 months (3–25). Results: Rituximab induced complete remission in 2 MCD patients and partial remission in 3 patients. Proteinuria was reduced by 86.8% (42.9–95.2) 3 months and by 73.0% (60.1–95.5) 6 months after therapy. In 1 patient with severe FSGS, partial remission was not evident before 6 months after rituximab treatment. Relapses occurred in 2 patients. No severe adverse events related to rituximab were observed. Conclusion: Our findings suggest that B cell-directed therapies are novel treatment options for adults with refractory NS. Response to rituximab varied, with MCD patients exhibiting a faster and more pronounced response compared to FSGS patients.

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          Adult minimal-change disease: clinical characteristics, treatment, and outcomes.

          Jennifer Crew, J Busch, B T Stokes … (2007)
          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.
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            Rituximab for idiopathic membranous nephropathy.

            Mario Bontempelli, Carlos Chiurchiu, Giuseppe Remuzzi … (2002)
            Treatments for idiopathic membranous nephropathy, a common cause of nephrotic syndrome, can be very toxic. In view of the pathogenic potential of B cells in this disease, we studied the effects of four weekly infusions of rituximab (375 mg/m(2)-- the monoclonal antibody to B-cell antigen CD20--in eight patients who had idiopathic membranous nephropathy with persistent nephrotic syndrome. At weeks 4 and 20, urinary protein decreased from mean (SE) 8.6 g/24 h (1.4) to 3.8 (0.8) and 3.7 (0.9), respectively (p<0.0001). At week 20, albuminuria and albumin fractional clearance decreased by 70% and 65%, and serum albumin increased by 31%. CD20 B lymphocytes fell below normal ranges up to study end. The short-term risk-benefit profile of rituximab seems more favourable to that of any other immunosuppressive drug used to treat idiopathic membranous nephropathy.
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              Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial.

              Alberto Edefonti, Elisa Benetti, Andrea Pasini … (2011)
              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. This 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. Fifty-four children (mean age 11 ± 4 years) with INS dependent on prednisone and calcineurin inhibitors for >12 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 = 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P < 0.001); 50% of RTX cases were in stable remission without drugs after 9 months. 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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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2012
                Publication date (Print): May 2012
                Publication date (Electronic): 26 January 2012
                Volume: 120
                Issue: 2
                Pages: c79-c85
                Affiliations
                aRenal Division, Department of Medicine and Center for Molecular Medicine, and bCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
                Author notes
                *Christine E. Kurschat, University Hospital of Cologne, Kerpener Strasse 62, DE–50937 Cologne (Germany), Tel. +49 221 478 89032, E-Mail christine.kurschat@uk-koeln.de
                Article
                Publisher ID: 335142 Other ID: Nephron Clin Pract 2012;120:c79–c85
                DOI: 10.1159/000335142
                PubMed ID: 22286071
                SO-VID: 856ab722-76e4-4bab-9e49-b8e10ef28234
                Copyright © © 2012 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 14 September 2011
                Date accepted : 10 November 2011
                Page count
                Figures: 1, Tables: 1, Pages: 7
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Minimal change disease,Nephrotic syndrome,Rituximab,Focal-segmental glomerulosclerosis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Minimal change disease, Nephrotic syndrome, Rituximab, Focal-segmental glomerulosclerosis

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