Skip to main content
Log in

Rituximab for Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome in Adults: A Retrospective, Multicenter Study in Spain

  • Original Research Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Background

Patients with difficult-to-treat idiopathic nephrotic syndrome (INS), steroid-dependent nephrotic syndrome (SDNS), or frequently relapsing nephrotic syndrome (FRNS) require long-term immunosuppressive therapy. Rituximab offers an alternative treatment for patients with disease that has not responded to multiple therapies.

Objective

Our objective was to determine the efficacy and safety of rituximab in adult patients with difficult-to-treat (SDNS or FRNS) INS.

Methods

We performed a retrospective multicenter study that included 50 adults with difficult-to-treat INS in six Spanish centers. All patients were treated with steroids in combination with another immunosuppressant: 28 patients received rituximab as the additional treatment (rituximab group), and the other 22 patients not treated with rituximab served as the control group.

Results

Of the patients treated with rituximab, 23 (82%) experienced complete remission, 20 (71%) had no relapses after receiving rituximab, and 13 (46%) did not receive any immunosuppressant. Of those in the control group, 14 (63%) experienced complete remission, including eight without immunosuppressants (29%). The rituximab group experienced highly significant reductions in total number of relapses per year (p < 0.001), proteinuria (p = 0.03), steroid doses (p = 0.002), and tacrolimus doses (p = 0.001). Mean follow-up after rituximab was 31 ± 26 months (range 8–86). The need for steroids and other immunosuppressants to achieve sustained remission was lower in the rituximab group than in the control group.

Conclusions

Rituximab treatment was safe and well tolerated. It effectively reduced the incidence of relapses and need for maintenance immunosuppressive therapy in adults with difficult-to-treat INS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. International study of kidney disease in children. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. Pediatr. 1981;98(4):561–4.

  2. Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, et al. Adult minimal-change disease clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007;2:445–53.

    Article  CAS  PubMed  Google Scholar 

  3. Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol 2014;25(4):850–63.

  4. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol. 2004;15:2169–77.

    Article  PubMed  Google Scholar 

  5. Kyrieleis HAC, Löwik MM, Pronk I, Cruysberg HRM, Kremer JAM, Oyen WJG, et al. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol. 2009;4:1593–600.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bargman JM. Management of minimal lesion glomerulonephritis: evidence-based recommendations. Kidney Int. 1999;55(Suppl 70):S3–16.

    Article  Google Scholar 

  7. Kemper MJ, Meyer-Jark T, Lilova M, Müller-Wiefel DE. Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol. 2003;60:242–7.

    Article  CAS  PubMed  Google Scholar 

  8. Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Ravà L, Ruggiero B, Emma F, Vivarelli M. B Cell reconstitution after rituximab treatment in idiopathic nephrotic syndrome. J Am Soc Nephrol. 2016;27(6):1811–22.

    Article  PubMed  Google Scholar 

  9. Makiko N, Koichi K, Nozu K, Matsuoka A, et al. Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol. 2008;23:481–5.

    Article  Google Scholar 

  10. Jayne D. Role of rituximab therapy in glomerulonephritis. J Am Soc Nephrol. 2010;21:14–7.

    Article  CAS  PubMed  Google Scholar 

  11. Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, et al. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2014;384:1273–81.

    Article  CAS  PubMed  Google Scholar 

  12. Gilbert RD, Hulse E, Rigden S. Rituximab therapy for steroid-dependent minimal change nephrotic syndrome. Pediatr Nephrol. 2006;21:1698–700.

    Article  PubMed  Google Scholar 

  13. Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, et al. Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome. Pediatr Nephrol. 2013;28:257–64.

    Article  PubMed  Google Scholar 

  14. Tellier S, Brochard K, Garnier A, Bandin F, Llanas B, Guigonis V, et al. Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome. Pediatr Nephrol. 2013;28:911–8.

    Article  PubMed  Google Scholar 

  15. Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, et al. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013;84:1025–33.

    Article  CAS  PubMed  Google Scholar 

  16. Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome multicentric report. Clin J Am Soc Nephrol. 2010;5:2207–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. François 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;49:158–61.

    Article  PubMed  Google Scholar 

  18. Iwabuchi Y, Takei T, Moriyama T, Itabashi M, Nitta K. Long-term prognosis of adult patients with steroid-dependent minimal change nephrotic syndrome following rituximab treatment. Medicine (Baltimore). 2014;93(29):e300.

    Article  CAS  Google Scholar 

  19. Bruchfeld A, Benedek S, Hilderman M, Medin C, Snaedal-Jonsdottir S, Korkeila M. Rituximab for minimal change disease in adults Long-term follow-up. Nephrol Dial Transpl. 2014;29:851–6.

    Article  CAS  Google Scholar 

  20. Guitard J, Hebral A-L, Fakhouri F, Joly D, Daugas E, Rivalan J, et al. Rituximab for minimal-change nephrotic syndrome in adulthood predictive factors for response, long-term outcomes and tolerance. Nephrol Dial Transpl. 2014;2084:1–8.

    Google Scholar 

  21. Munyentwali H, Bouachi K, Audard V, Remy P, Lang P, Mojaat R, et al. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. Kidney Int. 2013;83:511–6.

    Article  CAS  PubMed  Google Scholar 

  22. Al Kronbichler. Kerschbaum J, Fernandez-Fresnedo G, Hoxha E, Kurschat CE, Busch M, Bruchfeld A, Mayer G, Rudnicki M. Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis a systematic review. Am J Nephrol. 2014;39(4):322–30.

    Article  Google Scholar 

  23. KDIGO Guidelines. Chapter 6 Idiopathic focal segmental glomerulosclerosis in adults. Kidney Int Suppl 2012;2(2):181–185.

  24. KDIGO Guidelines. Chapter 3 Steroid-sensitive nephrotic syndrome in children. Kidney Int Suppl 2012;2(2):163–171.

  25. Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–72.

    Article  CAS  PubMed  Google Scholar 

  26. Smith GC. Is there a role for rituximab in the treatment of idiopathic childhood nephrotic syndrome? Pediatr Nephrol. 2007;22:893–8.

    Article  PubMed  Google Scholar 

  27. Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, et al. Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol. 2009;24:1321–8.

    Article  PubMed  Google Scholar 

  28. Takei T, Itabashi M, Moriyama T, Kojima C, Shiohira S, Shimizu A, et al. Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults. Nephrol Dial Transplant. 2013;28:1225–32.

    Article  CAS  PubMed  Google Scholar 

  29. Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, et al. Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant. 2012;27:1910–5.

    Article  CAS  PubMed  Google Scholar 

  30. Nakayama M, Kamei K, Nozu K, Matsuoka K, Nakagawa A, Sako M, et al. Rituximab for refractory focal segmental glomerulosclerosis. Pediatr Nephrol. 2008;23:481–5.

    Article  PubMed  Google Scholar 

  31. Kronbichler A, Bruchfeld A. Rituximab in adult minimal change disease and focal segmental glomerulosclerosis. Nephron Clin Pract. 2014;128(3–4):277–82.

    Article  CAS  PubMed  Google Scholar 

  32. Sinha A, Bagga A. Rituximab therapy in nephrotic syndrome implications for patients’ management. Nat Rev Nephrol. 2013;9:154–69.

    Article  CAS  PubMed  Google Scholar 

  33. Kumar J, Shatat IF, Skversky AL, Woroniecki RP, Del Rio M, Perelstein EM, et al. Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis. Pediatr Nephrol. 2013;28:333–8.

    Article  PubMed  Google Scholar 

  34. Sellier-Leclerc A-L, Baudouin V, Kwon T, Macher M-A, Guérin V, Lapillonne H, et al. Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood–follow-up after CD19 recovery. Nephrol Dial Transplant. 2012;27:1083–9.

    Article  CAS  PubMed  Google Scholar 

  35. Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, et al. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome a multicentric series of 22 cases. Pediatr Nephrol. 2008;23:1269–79.

    Article  PubMed  Google Scholar 

  36. Fervenza FC, Abraham RS, Erickson SB, Irazabal MV, Eirin A, Specks U, et al. Rituximab therapy in idiopathic membranous nephropathy a 2-year study. Clin J Am Soc Nephrol. 2010;5:2188–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fornoni A, Sageshima J, Wei C, Merscher-Gomez S, Aguillon-Prada R, Jauregui AN, et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci Transl Med. 2011;3:85ra46.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kari JA, El-Morshedy SM, El-Desoky S, Alshaya HO, Rahim KA, Edrees BM. Rituximab for refractory cases of childhood nephrotic syndrome. Pediatr Nephrol. 2011;26:733–7.

    Article  PubMed  Google Scholar 

  39. Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome a randomized controlled trial. Clin J Am Soc Nephrol. 2011;6:1308–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors especially thank all the patients who participated in this study. We also thank Ignasi Gish for statistical analysis and Ricard Pellejero for his bibliographic assistance.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Montserrat Díaz-Encarnación.

Ethics declarations

Funding

No funding was received for the conduct of this study or the preparation of this manuscript.

Conflicts of Interest

ID, AH, LQ, BR, EI, JD, MP, JB, and MD have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

DaSilva, I., Huerta, A., Quintana, L. et al. Rituximab for Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome in Adults: A Retrospective, Multicenter Study in Spain. BioDrugs 31, 239–249 (2017). https://doi.org/10.1007/s40259-017-0221-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-017-0221-x

Navigation