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Vol. 120, No. 2, 2012
Issue release date: May 2012
Nephron Clin Pract 2012;120:c79–c85
(DOI:10.1159/000335142)

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

Kisner T.a · Burst V.a · Teschner S.a · Benzing T.a, b · Kurschat C.E.a, b
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
email Corresponding Author

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.


 Outline


 goto top of outline Key Words

  • Rituximab
  • Nephrotic syndrome
  • Minimal change disease
  • Focal-segmental glomerulosclerosis

 goto top of outline 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.

Copyright © 2012 S. Karger AG, Basel


goto top of outline Introduction

The treatment of idiopathic focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) resistant to immunosuppressive therapy or frequently relapsing remains a challenge not only for pediatric but also for adult nephrologists [1,2]. In MCD, most adult patients initially respond to steroid treatment but prevention of relapse is often difficult. Cyclosporine A (CsA) has proven its efficacy in sustaining partial or complete remission [3,4]. Two major problems arise with long-term CsA treatment: chronic nephrotoxicity [5] and relapse of proteinuria after CsA withdrawal [1]. The variety of toxic side effects has led to a search for alternative immunosuppressive therapy.

Current concepts suggest that not only T cells but also B cells are actively involved in the pathogenesis of MCD and FSGS [6,7] and, in particular, the as yet unidentified circulating permeability factor which may be released directly from B cells or secondary to an aberrant cross-talk between T and B cells. Rituximab, a chimeric monoclonal antibody inhibiting CD20-mediated B cell proliferation and differentiation, was first used for treatment of nephrotic syndrome (NS) by Remuzzi et al. [8] in adult patients with idiopathic membranous nephropathy. Recently, rituximab has become a new therapeutic strategy primarily in children with steroid-resistant and steroid-dependent NS [7,9,10,11,12,13,14,15]. In adult patients, rituximab has proven its efficacy in reducing proteinuria of renal transplant patients with relapsing FSGS in the transplant [16]. The first case report using rituximab for relapsing MCD in adults was published by François et al. [17]. Since then, information about the efficacy of rituximab treatment in adults with MCD and FSGS has remained limited [11,18,19,20,21,22,23].

We report on 5 adult patients treated successfully with rituximab for severe FSGS (2 patients) and for relapsing MCD (3 patients). All patients had not responded to conventional immunosuppressive therapy, but rituximab treatment remarkably induced partial or complete remission.

 

goto top of outline Subjects and Methods

goto top of outline Patients

Five adult patients were treated with rituximab in our outpatient department between January 2009 and March 2011 for severe proteinuria due to FSGS or relapsing MCD resistant to standard corticosteroid and immunosuppressive therapy (table 1). This study was reviewed and approved by the Institutional Review Board of the University of Cologne.

TAB01
Table 1. Main clinical and laboratory data of individual patients and follow-up of proteinuria and immunosuppressive maintenance therapy after rituximab treatment: data at 6 months were available in 3 patients and data at 9 months in 2 patients

Patients fulfilled the following criteria: (1) biopsy-proven FSGS or MCD characterized by proteinuria >1 g/day, (2) course of the disease resistant to corticosteroid treatment and to other previous immunosuppressive treatments, (3) no systemic disease, comorbid conditions or concomitant infections, and (4) no previous rituximab treatment. For each patient, demographic data and clinical data were collected at baseline before starting rituximab therapy and at 3, 6 and 9 months’ follow-up.

Patients were defined to have steroid-resistant disease if the urine protein/creatinine ratio did not decline significantly after treatment with prednisone ≥1 mg/kg per day for 4 months. Patients were steroid-dependent if they experienced at least one relapse while steroid tapering, while receiving oral prednisone at 5 mg/day or after its discontinuation.

Complete remission was defined as a urine protein/creatinine ratio of <300 mg/g creatinine. Partial remission was defined as a urine protein/creatinine ratio between 300 and 3,500 mg/g creatinine or as a reduction of proteinuria of ≥50%.

goto top of outline Treatment

Rituximab was administered i.v. during 3–4 h after premedication (1 g oral paracetamol, 8 mg dexamethasone i.v. and 4 mg dimetindene i.v.). Patients were closely monitored for infusion-related reactions such as headache, chills, fever, rash, or hypotension. Four patients received a second dose within 14–21 days according to regimens previously reported to control disease [18,19]. Patient 3 received only one dose. Patient 5 was treated with two doses of 375 mg/m2. In our study, we used different treatment regimens due to the fact that specific information on the most effective dose regimen in MCD and FSGS patients is lacking. To date, the safety profile of rituximab still remains unclear. Known severe side effects such as hypogammaglobulinemia, reactivation of JC virus, Pneumocystis jirovecii pneumonia or progressive multifocal leukoencephalopathy have not been detected in our patients so far.

 

goto top of outline Results

Between January 2009 and March 2011 five patients (3 male, 2 female) received rituximab therapy in our outpatient department due to FSGS or MCD otherwise unresponsive to immunosuppressive treatment (table 1). Mean duration of disease prior to rituximab treatment was 59.2 ± 64.88 months. In all patients, several different immunosuppressive regimens had been administered without sustained success. Mean serum creatinine level at baseline prior to rituximab treatment was 1.07 ± 0.33 mg/dl, and mean eGFR (MDRD formula) was 70.20 ± 19.40 ml/min/1.73 m2. The duration of proteinuria >1 g/day prior to rituximab administration was 14 months in 1 patient, 12 months in 1 patient and 1 month in 3 patients. In the 2 female patients (patient 1 and patient 5) with a history of relapsing MCD for more than 8 years, we administered rituximab already at urine protein concentrations <3.5 g/day in order to treat the next upcoming relapse as early as possible.

Rituximab therapy lead to a complete B cell depletion in all patients as demonstrated in fluorescence-activated cell sorting (FACS) analyses. The median follow-up after the first rituximab infusion was 8 months (3–25).

Maintenance therapy after rituximab infusion consisted of MMF/CsA/Pred in 2 patients, MMF/Tac/Pred in 1, AZA/CsA/Pred in 1, and CsA/Pred in 1 (table 1). In all cases, the steroid dose was successfully tapered after rituximab administration.

goto top of outline Response at 3 Months’ Follow-Up

At 3 months, all patients showed a response to the rituximab infusion (fig. 1). We observed an overall decline in proteinuria of 79.7 ± 21.06% compared to initial levels. In all patients, proteinuria levels decreased by more than 40% of initial levels [median 86.8 (42.9–95.2)] (table 1). Two patients showed complete remission and 2 patients had partial remission. In 1 patient with severe FSGS, rituximab treatment decreased proteinuria by 42.9% after 3 months’ and by 60.1% after 6 months’ follow-up. In this patient, partial remission was achieved later compared to the remaining 4 patients, suggesting that patients respond differently to rituximab therapy.

FIG01
Fig. 1. Course of proteinuria before and after rituximab therapy. Patient numbers are attributed according to the date of their first rituximab therapy. In patients 1, 2, 4 and 5, two consecutive doses of rituximab were administered within 14–21 days.

goto top of outline Relapse/Retreatment

Patient 1 relapsed 23 months after rituximab treatment upon tapering of CsA. A consecutive increase in CsA dose and short-term increase in steroid dose was sufficient to stop proteinuria (fig. 1). Patient 2 received a second course of two rituximab doses due to a relapse 9 months later, after having reached partial remission initially.

Taken together, our data suggest that B cell-directed therapies may provide a very promising alternative for the treatment of FSGS and MCD in adults resistant to conventional therapy.

 

goto top of outline Discussion

Treatment of FSGS resistant to standard immunosuppressive treatment as well as control of relapsing MCD in adults remains a therapeutic challenge for nephrologists. New strategies in managing these patients have emerged recently. Since the first report on successful administration of rituximab in childhood NS [13], the use of rituximab in pediatric patients with NS is increasing (for a review, see [7]). A randomized controlled trial on short-term effects of rituximab use in 54 children with idiopathic NS demonstrated a 70% decrease of 3-month proteinuria compared to standard immunosuppressive treatment [24]. Prytula et al. [25] reported a benefit of rituximab treatment in only 44% of children with steroid-resistant NS. In the study by Gulati et al. [12], only 27.2% of patients reached full remission, 21.2% had partial remission, and 51.5% had no response. But data on adult patients are still limited [11,17,18,19,20,21,22,23]. Fernandez-Fresnedo et al. [21] observed a positive effect on proteinuria in only 3 of 8 adult patients with severe steroid-resistant FSGS in Spain. Recently, Sugiura et al. [22] showed that MCD patients responded well to a single rituximab dose whereas FSGS, membranous nephropathy, IgA nephropathy, and membranoproliferative glomerulonephritis patients responded less convincingly. These studies illustrate that randomized controlled trials are important in order to establish recommendations for rituximab use in NS, to prove its efficacy, its safety and its cost effectiveness. They are crucial to avoid publication bias.

The pathogenesis of adult FSGS is still not completely understood. Unlike in children with steroid-resistant FSGS, where a significant proportion of patients exhibit mutations in genes coding for components of the glomerular filtration barrier, FSGS in adults is believed to involve a circulating ‘FSGS factor’ that is yet unidentified [26]. Recent findings have illustrated that not only T cells but also B cells are actively involved in the pathogenesis of idiopathic NS [6,7]. In the past, FSGS was thought to be only T cell mediated, resulting in the secretion of a cytokine toxic to glomeruli [for a review, see [27]). Current concepts underline the role of an as yet unidentified circulating permeability factor which may be released directly from B cells or secondary to an aberrant cross-talk between T and B cells. Since not all FSGS patients respond equally well to rituximab treatment, this underlines the diversity of clinical course and outcome in FSGS patients and suggests the existence of different subgroups within these patients.

Although treatment options for MCD are the same as for FSGS, convincing evidence is still lacking that both MCD and FSGS are different stages of the same disease [27]. In our cohort of 3 MCD patients with relapsing disease, response to rituximab was much faster and more pronounced as compared to the 2 patients with FSGS. Although the patient number in our study is very limited, it is tempting to speculate that response to rituximab therapy might be better in relapsing MCD. FSGS patients are usually treated with rituximab during later stages of their disease possibly also affecting efficacy of rituximab treatment.

The monoclonal anti-CD20 antibody rituximab successfully depletes B cells from the circulation. The available data on rituximab treatment in FSGS and MCD describes different regimens of B cell depletion. Data from a German registry of 27 pediatric patients treated with rituximab showed no difference between a single dose of rituximab versus three or four infusions in terms of duration of remission [7]. In adults, a single infusion of rituximab (375 mg/m2) is usually capable of completely suppressing CD19 counts [20]. The question whether rituximab should be administered upon recovery of CD19 counts, regardless of clinical symptoms, has not been answered yet. Relapse rates after rituximab treatment depend on the degree of initial B cell depletion and/or on the rate of B cell recovery. In 22 pediatric patients with steroid-sensitive NS, the relapse rate was related to the initial amount of B cell depletion [28]. Interestingly, some patients did not relapse despite full recovery of B cells. The question of rituximab dosage and number of courses as well as the duration of treatment and the necessity for repeated treatment in proteinuric kidney disease can only be answered by prospective randomized trials.

Maintaining remission after successful rituximab treatment is a challenge. The use of MMF in small retrospective as well as prospective studies is promising in pediatric patients [29,30]. A large prospective trial on the use of MMF in FSGS patients after rituximab administration is currently conducted at the NIH [31].

There is a selection bias for patients treated with rituximab since this therapy is used as a rescue option for patients otherwise unresponsive to current immunosuppressive treatment. Rituximab is usually well tolerated, but no data are available on long-term effects. Severe side effects such as infection, hypogammaglobulinemia, P. jirovecii pneumonia, reactivation of JC virus, progressive multifocal leukoencephalopathy, cardiomyopathy, pancolitis, and lung fibrosis have been reported [15,25,32]. Thus, potential benefits in FSGS and MCD patients have to be balanced against yet unknown negative long-term effects of rituximab.

Up to now, large prospective randomized trials on rituximab treatment for FSGS and MCD in adults are lacking. Promising results have been published mainly as case reports bearing a potential publication bias due to patient selection.

In our report we analyzed all patients treated with rituximab for refractory proteinuric kidney disease in our outpatient department in order to anticipate such reporting bias. Nevertheless, the number of patients in this observational study is very limited. Rituximab was well tolerated and induced a sustained reduction of proteinuria in all 5 patients. One patient with severe FSGS responded to rituximab therapy significantly later compared to the other 4 patients. This observation suggests a differential response to rituximab therapy depending on the underlying course of disease.

The data on rituximab use in adults with FSGS or MCD published to date are promising but they illustrate the importance of controlled clinical trials necessary to generate reliable recommendations of rituximab use in adults with proteinuric kidney disease.

 

goto top of outline Disclosure Statement

The authors do not disclose any conflicts of interest.


 goto top of outline References
  1. Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, D’Agati V, Appel G: Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2007;2:445–453.
  2. Gbadegesin R, Lavin P, Foreman J, Winn M: Pathogenesis and therapy of focal segmental glomerulosclerosis: an update. Pediatr Nephrol 2011;26:1001–1015.
  3. Meyrier A: Treatment of idiopathic nephrosis by immunophillin modulation. Nephrol Dial Transplant 2003;18(suppl 6):vi79–vi86.

    External Resources

  4. Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, Ponticelli C, Saito T, Choukroun G, Nachman P, Praga M, Yoshikawa N: Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 2007;72:1429–1447.
  5. Chapman JR: Chronic calcineurin inhibitor nephrotoxicity – lest we forget. Am J Transplant 2011;11:693–697.
  6. Kemper MJ, Meyer-Jark T, Lilova M, Muller-Wiefel DE: Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 2003;60:242–247.
  7. van Husen M, Kemper MJ: New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 2011;26:881–892.
  8. Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P: Rituximab for idiopathic membranous nephropathy. Lancet 2002;360:923–924.
  9. Bagga A, Sinha A, Moudgil A: Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 2007;356:2751–2752.
  10. Nakayama M, Kamei K, Nozu K, Matsuoka K, Nakagawa A, Sako M, Iijima K: Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol 2008;23:481–485.
  11. Kurosu N, Sugiura H, Iwasaki C, Asamiya Y, Kojima C, Moriyama T, Itabashi M, Tsukada M, Takei T, Ogawa T, Yoshida T, Uchida K, Tsuchiya K, Nitta K: Successful use of single-dose rituximab for the maintenance of remission in a patient with steroid-resistant nephrotic syndrome. Intern Med 2009;48:1901–1904.
  12. Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil A, Bagga A: Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 2010;5:2207–2212.
  13. Benz K, Dotsch J, Rascher W, Stachel D: Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 2004;19:794–797.
  14. Haffner D, Fischer DC: Nephrotic syndrome and rituximab: facts and perspectives. Pediatr Nephrol 2009;24:1433–1438.
  15. Sellier-Leclerc AL, Macher MA, Loirat C, Guerin V, Watier H, Peuchmaur M, Baudouin V, Deschenes G: Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 2010;25:1109–1115.
  16. Ponticelli C, Glassock RJ: Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 2010;5:2363–2372.
  17. Francois H, Daugas E, Bensman A, Ronco P: Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis 2007;49:158–161.
  18. Hofstra JM, Deegens JK, Wetzels JF: Rituximab: effective treatment for severe steroid-dependent minimal change nephrotic syndrome? Nephrol Dial Transplant 2007;22:2100–2102.
  19. Peters HP, van de Kar NC, Wetzels JF: Rituximab in minimal change nephropathy and focal segmental glomerulosclerosis: report of four cases and review of the literature. Neth J Med 2008;66:408–415.
  20. Sawara Y, Itabashi M, Kojima C, Tabata H, Kamei D, Kawanishi K, Moriyama T, Sugiura H, Tsukada M, Takei T, Ogawa T, Yoshida T, Arai J, Uchida K, Tsuchiya K, Nitta K: Successful therapeutic use of a single-dose of rituximab on relapse in adults with minimal change nephrotic syndrome. Clin Nephrol 2009;72:69–72.
  21. Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N, Egido J, Praga M: Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2009;4:1317–1323.
  22. Sugiura H, Takei T, Itabashi M, Tsukada M, Moriyama T, Kojima C, Shiohira T, Shimizu A, Tsuruta Y, Amemiya N, Ogawa T, Uchida K, Tsuchiya K, Nitta K: Effect of single-dose rituximab on primary glomerular diseases. Nephron Clin Pract 2011;117:c98–c105.
  23. Yang T, Nast CC, Vo A, Jordan SC: Rapid remission of steroid and mycophenolate mofetil (MMF)-resistant minimal change nephrotic syndrome after rituximab therapy. Nephrol Dial Transplant 2008;23:377–380.
  24. Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM: Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol 2011;6:1308–1315.
  25. Prytula A, Iijima K, Kamei K, Geary D, Gottlich E, Majeed A, Taylor M, Marks SD, Tuchman S, Camilla R, Ognjanovic M, Filler G, Smith G, Tullus K: Rituximab in refractory nephrotic syndrome. Pediatr Nephrol 2010;25:461–468.
  26. Meyrier A: An update on the treatment options for focal segmental glomerulosclerosis. Expert Opin Pharmacother 2009;10:615–628.
  27. Meyrier AY: Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? Kidney Int 2009;76:487–491.
  28. Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F: Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 2008;23:1269–1279.
  29. Ito S, Kamei K, Ogura M, Sato M, Fujimaru T, Ishikawa T, Udagawa T, Iijima K: Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol 2011;26:1823–1828.
  30. Filler G, Huang SH, Sharma AP: Should we consider mmf therapy after rituximab for nephrotic syndrome? Pediatr Nephrol 2011;26:1759–1762.
  31. Appel AS, Appel GB: An update on the use of mycophenolate mofetil in lupus nephritis and other primary glomerular diseases. Nat Clin Pract Nephrol 2009;5:132–142.
  32. Kamei K, Ito S, Iijima K: Severe respiratory adverse events associated with rituximab infusion. Pediatr Nephrol 2010;25:1193.

 goto top of outline Author Contacts

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


 goto top of outline Article Information

Received: September 14, 2011
Accepted: November 10, 2011
Published online: January 26, 2012
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 1, Number of References : 32


 goto top of outline Publication Details

Nephron Clinical Practice

Vol. 120, No. 2, Year 2012 (Cover Date: May 2012)

Journal Editor: El Nahas M. (Sheffield)
ISSN: NIL (Print), eISSN: 1660-2110 (Online)

For additional information: http://www.karger.com/NEC


Copyright / Drug Dosage / Disclaimer

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

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.



 goto top of outline Author Contacts

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


 goto top of outline Article Information

Received: September 14, 2011
Accepted: November 10, 2011
Published online: January 26, 2012
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 1, Number of References : 32


 goto top of outline Publication Details

Nephron Clinical Practice

Vol. 120, No. 2, Year 2012 (Cover Date: May 2012)

Journal Editor: El Nahas M. (Sheffield)
ISSN: NIL (Print), eISSN: 1660-2110 (Online)

For additional information: http://www.karger.com/NEC


Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

References

  1. Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, D’Agati V, Appel G: Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2007;2:445–453.
  2. Gbadegesin R, Lavin P, Foreman J, Winn M: Pathogenesis and therapy of focal segmental glomerulosclerosis: an update. Pediatr Nephrol 2011;26:1001–1015.
  3. Meyrier A: Treatment of idiopathic nephrosis by immunophillin modulation. Nephrol Dial Transplant 2003;18(suppl 6):vi79–vi86.

    External Resources

  4. Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, Ponticelli C, Saito T, Choukroun G, Nachman P, Praga M, Yoshikawa N: Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int 2007;72:1429–1447.
  5. Chapman JR: Chronic calcineurin inhibitor nephrotoxicity – lest we forget. Am J Transplant 2011;11:693–697.
  6. Kemper MJ, Meyer-Jark T, Lilova M, Muller-Wiefel DE: Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 2003;60:242–247.
  7. van Husen M, Kemper MJ: New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 2011;26:881–892.
  8. Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P: Rituximab for idiopathic membranous nephropathy. Lancet 2002;360:923–924.
  9. Bagga A, Sinha A, Moudgil A: Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 2007;356:2751–2752.
  10. Nakayama M, Kamei K, Nozu K, Matsuoka K, Nakagawa A, Sako M, Iijima K: Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol 2008;23:481–485.
  11. Kurosu N, Sugiura H, Iwasaki C, Asamiya Y, Kojima C, Moriyama T, Itabashi M, Tsukada M, Takei T, Ogawa T, Yoshida T, Uchida K, Tsuchiya K, Nitta K: Successful use of single-dose rituximab for the maintenance of remission in a patient with steroid-resistant nephrotic syndrome. Intern Med 2009;48:1901–1904.
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