Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases

Abstract

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3–22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.

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References

  1. 1.

    Niaudet P (2004) Steroid-sensitive idiopathic nephrotic syndrome in children. In: Avner E, Harmon W, Niaudet P (eds) Pediatric Nephrology, 5th ed. Lippincot Williams & Wilkins, Philadelphia, pp 543–556

    Google Scholar 

  2. 2.

    Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grunfeld JP, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557

    Article  Google Scholar 

  3. 3.

    British Association for Paediatric Nephrology (1991) Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology. Lancet 337:1555–1557

    Article  Google Scholar 

  4. 4.

    Niaudet P (1992) Comparison of cyclosporin and chlorambucil in the treatment of steroid-dependent idiopathic nephrotic syndrome: a multicentre randomized controlled trial. The French Society of Paediatric Nephrology. Pediatr Nephrol 6:1–3

    CAS  Article  Google Scholar 

  5. 5.

    Bagga A, Hari P, Moudgil A, Jordan SC (2003) Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 42:1114–1120

    CAS  Article  Google Scholar 

  6. 6.

    Report of Arbeitsgemeinschaft fur Pädiatrische Nephrologie (1987) Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft fur Padiatrische Nephrologie. Arch Dis Child 62:1102–1106

    Article  Google Scholar 

  7. 7.

    Dötsch J, Müller-Wiefel DE, Kemper MJ (2008) Rituximab: is replacement of cyclophosphamide and calcineurin inhibitors in steroid-dependent nephrotic syndrome possible? Pediatr Nephrol 23:3–7

    Article  Google Scholar 

  8. 8.

    Benz K, Dötsch J, Rascher W, Stachel D (2004) Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 19:794–797

    Article  Google Scholar 

  9. 9.

    Pescovitz MD, Book BK, Sidner RA (2006) Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med 354:1961–1963

    CAS  Article  Google Scholar 

  10. 10.

    Nozu K, Iijima K, Fujisawa M, Nakagawa A, Yoshikawa N, Matsuo M (2005) Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome. Pediatr Nephrol 20:1660–1663

    Article  Google Scholar 

  11. 11.

    Bagga A, Sinha A, Moudgil A (2007) Rituximab in patients with the steroid-resistant nephrotic syndrome. N Engl J Med 356:2751–2752

    CAS  Article  Google Scholar 

  12. 12.

    Francois H, Daugas E, Bensman A, Ronco P (2007) Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis 49:158–161

    CAS  Article  Google Scholar 

  13. 13.

    Gilbert RD, Hulse E, Rigden S (2006) Rituximab therapy for steroid-dependent minimal change nephrotic syndrome. Pediatr Nephrol 21:1698–1700

    Article  Google Scholar 

  14. 14.

    Hofstra JM, Deegens JK, Wetzels JF (2007) Rituximab: effective treatment for severe steroid-dependent minimal change nephrotic syndrome? Nephrol Dial Transplant 22:2100–2102

    Article  Google Scholar 

  15. 15.

    Nakayama M, Kamei K, Nozu K, Matsuoka K, Nakagawa A, Sako M, Iijima K (2008) Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol 23:481–485

    Article  Google Scholar 

  16. 16.

    Smith GC (2007) Is there a role for rituximab in the treatment of idiopathic childhood nephrotic syndrome? Pediatr Nephrol 22:893–898

    Article  Google Scholar 

  17. 17.

    Yang T, Nast CC, Vo A, Jordan SC (2008) Rapid remission of steroid and mycophenolate mofetil (MMF) resistant minimal change nephrotic syndrome after rituximab therapy. Nephrol Dial Transplant 23:377–380

    Article  Google Scholar 

  18. 18.

    Gossmann J, Scheuermann EH, Porubsky S, Kachel HG, Geiger H, Hauser IA (2007) Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis. Transpl Int 20:558–562

    Article  Google Scholar 

  19. 19.

    Hristea D, Hadaya K, Marangon N, Buhler L, Villard J, Morel P, Martin PY (2007) Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab. Transpl Int 20:102–105

    CAS  Article  Google Scholar 

  20. 20.

    Kamar N, Faguer S, Esposito L, Guitard J, Nogier MB, Durand D, Rostaing L (2007) Treatment of focal segmental glomerular sclerosis with rituximab: 2 case reports. Clin Nephrol 67:250–254

    CAS  Article  Google Scholar 

  21. 21.

    Yabu JM, Ho B, Scandling JD, Vincenti F (2008) Rituximab Failed to Improve Nephrotic Syndrome in Renal Transplant Patients With Recurrent Focal Segmental Glomerulosclerosis. Am J Transplant 8:222–227

    CAS  Google Scholar 

  22. 22.

    Berard E, Broyer M, Dehennault M, Dumas R, Eckart P, Fischbach M, Loirat C, Martinat L, Pediatric Society of Nephrology (2005) Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic guideline proposed by the Pediatric Society of Nephrology. Nephrol Ther 1:150–156

    Article  Google Scholar 

  23. 23.

    Meyer TN, Thaiss F, Stahl RA (2007) Immunoadsorption and rituximab therapy in a second living-related kidney transplant patient with recurrent focal segmental glomerulosclerosis. Transpl Int 20:1066–1071

    CAS  Article  Google Scholar 

  24. 24.

    El-Firjani A, Hoar S, Karpinski J, Bell R, Deschenes MJ, Knoll GA (2008) Post-transplant focal segmental glomerulosclerosis refractory to plasmapheresis and rituximab therapy. Nephrol Dial Transplant 23:425

    Article  Google Scholar 

  25. 25.

    Marks SD, McGraw M (2007) Does rituximab treat recurrent focal segmental glomerulosclerosis post-renal transplantation? Pediatr Nephrol 22:158–160

    Article  Google Scholar 

  26. 26.

    Fervenza FC, Cosio FG, Erickson SB, Specks U, Herzenberg AM, Dillon JJ, Leung N, Cohen IM, Wochos DN, Bergstralh E, Hladunewich M, Cattran DC (2008) Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 73:117–125

    CAS  Article  Google Scholar 

  27. 27.

    Kimby E (2005) Tolerability and safety of rituximab (MabThera). Cancer Treat Rev 31:456–473

    CAS  Article  Google Scholar 

  28. 28.

    Kolstad A, Holte H, Fossa A, Lauritzsen GF, Gaustad P, Torfoss D (2007) Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOEP-14 regimen. Haematologica 92:139–140

    CAS  Article  Google Scholar 

  29. 29.

    Motto DG, Williams JA, Boxer LA (2002) Rituximab for refractory childhood autoimmune hemolytic anemia. Isr Med Assoc J 4:1006–1008

    CAS  PubMed  Google Scholar 

  30. 30.

    Freim Wahl SG, Folvik MR, Torp SH (2007) Progressive multifocal leukoencephalopathy in a lymphoma patient with complete remission after treatment with cytostatics and rituximab: case report and review of the literature. Clin Neuropathol 26:68–73

    CAS  Article  Google Scholar 

  31. 31.

    Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y, Hurault de Ligny B, Niaudet P, Charpentier B, Soulillou JP (1994) Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N Engl J Med 330:7–14

    CAS  Article  Google Scholar 

  32. 32.

    Dantal J, Godfrin Y, Koll R, Perretto S, Naulet J, Bouhours JF, Soulillou JP (1998) Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. J Am Soc Nephrol 9:1709–1715

    CAS  PubMed  Google Scholar 

  33. 33.

    Habib R, Girardin E, Gagnadoux MF, Hinglais N, Levy M, Broyer M (1988) Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular “immune deposits”. Pediatr Nephrol 2:402–408

    CAS  Article  Google Scholar 

  34. 34.

    Hultin LE, Hausner MA, Hultin PM, Giorgi JV (1993) CD20 (pan-B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes. Cytometry 14:196–204

    CAS  Article  Google Scholar 

  35. 35.

    Sahali D, Pawlak A, Le Gouvello S, Lang P, Valanciute A, Remy P, Loirat C, Niaudet P, Bensman A, Guellaen G (2001) Transcriptional and post-transcriptional alterations of I kappa B alpha in active minimal-change nephrotic syndrome. J Am Soc Nephrol 12:1648–1658

    CAS  Google Scholar 

  36. 36.

    Mansour H, Cheval L, Elalouf JM, Aude JC, Alyanakian MA, Mougenot B, Doucet A, Deschenes G (2005) T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome. Kidney Int 67:2168–2177

    CAS  Article  Google Scholar 

  37. 37.

    Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B (2005) Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin’s lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res 65:264–276

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Pr. Thibault (Tours, France), Pr. Deschênes (Paris, France) and Dr. François (Paris, France) for helpful discussions and to C. Bahans for proofreading the manuscript.

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Correspondence to Vincent Guigonis.

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V. Guigonis and A. Dallocchio contributed equally to this article

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Guigonis, V., Dallocchio, A., Baudouin, V. et al. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23, 1269–1279 (2008). https://doi.org/10.1007/s00467-008-0814-1

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Keywords

  • Idiopathic nephrotic syndrome
  • Rituximab
  • CD19
  • B-cell depletion