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Cyclosporine versus mycophenolate mofetil for maintenance of remission of steroid-dependent nephrotic syndrome after a single infusion of rituximab

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Abstract

The efficacy of rituximab (RTX) as the sole therapy for preventing relapses of nephrotic syndrome (NS) is transient in most patients; therefore, the optimal therapy required for maintaining a successful response to a biological agent remains a challenge. We conducted a prospective study to compare the efficacy of cyclosporine (CsA) with that of mycophenolate mofetil (MMF) as maintenance therapy after a single infusion of RTX. Of 29 patients with persistent steroid-dependent NS despite the use of CsA and/or MMF, 13 without chronic nephrotoxicity continued CsA therapy, maintaining a 2-h post-dose CsA level of 400–500 ng/ml (CsA group). The remaining 16 were treated with MMF, maintaining a pre-dose level of 2–5 μg/ml of mycophenolic acid (MMF group). The median duration of CsA and MMF treatment was 18 and 19 months, respectively. Despite the mean number of relapses before RTX treatment being significantly lower in the MMF group than in the CsA group (2.3/year vs. 4.6/year, p < 0.01), treatment failure occurred more frequently in the MMF group (7/16) than in the CsA group (2/13). The rate of sustained remission was also significantly higher in the CsA group than in the MMF group (p < 0.05). Conclusion: In patients with severe steroid-dependent NS, CsA appears to be more effective than MMF for maintaining remission after a single infusion of RTX.

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Abbreviations

RTX:

Rituximab

CsA:

Cyclosporine

MMF:

Mycophenolate mofetil

MPA:

Mycophenolic acid

MZR:

Mizoribine

PSL:

Prednisolone

NS:

Nephrotic syndrome

CsAN:

Cyclosporine-induced nephrotoxicity

CAA:

Cyclosporine-associated arteriolopathy

STIL:

Striped tubulointerstitial lesions

eGFR:

Estimated glomerular filtration rate

References

  1. Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB (2003) Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 18:833–837

    Article  PubMed  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. Filler G, Huang SH, Sharma AP (2011) Should we consider MMF therapy after rituximab for nephrotic syndrome? Pediatr Nephrol 26:1759–1762

    Article  PubMed  Google Scholar 

  4. Filler G, Lepage N (2004) To what extent dose the understanding of pharmacokinetics of mycophenolate mofetil influence its prescription. Pediatr Nephrol 19:962–965

    PubMed  Google Scholar 

  5. Fujinaga S, Hirano D, Nishizaki N, Kamei K, Ito S, Ohtomo Y, Shimizu T, Kaneko K (2010) Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine. Pediatr Nephrol 25:539–544

    Article  PubMed  Google Scholar 

  6. Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670

    Article  PubMed  CAS  Google Scholar 

  7. Fujinaga S, Ohtomo Y, Umino D, Takemoto M, Shimizu T, Yamashiro Y, Kaneko K (2007) A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome. Pediatr Nephrol 22:71–76

    Article  PubMed  Google Scholar 

  8. Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104

    Article  PubMed  Google Scholar 

  9. 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 (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279

    Article  PubMed  Google Scholar 

  10. Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil A, Bagga A (2010) Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 5:2207–2212

    Article  PubMed  CAS  Google Scholar 

  11. Iijima K (2011) Rituximab for childhood refractory nephrotic syndrome. Pediatr Int 53:617–621

    Article  PubMed  CAS  Google Scholar 

  12. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805

    Article  PubMed  Google Scholar 

  13. Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Yata N, Ando T, Honda M (2010) Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 25:3956–3962

    Article  PubMed  CAS  Google Scholar 

  14. Ito S, Kamei K, Ogura M, Sato M, Fujimaru T, Ishikawa T, Udagawa T, Iijima K (2011) Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:1823–1828

    Article  PubMed  Google Scholar 

  15. Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328

    Article  PubMed  Google Scholar 

  16. Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dötsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27:1910–1915

    Article  PubMed  CAS  Google Scholar 

  17. Mendizábal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J (2005) Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome. Pediatr Nephrol 20:914–919

    Article  PubMed  Google Scholar 

  18. Nakamura T, Nozu K, Iijima K, Yoshikawa N, Morita Y, Yamamori M, Kako A, Matsuo M, Sakurai A, Okamura N, Ishikawa T, Okumura K, Sakaeda T (2007) Association of cumulative cyclosporine dose with its irreversible nephrotoxicity in Japanese patients with pediatric-onset autoimmune disease. Biol Pharm Bull 30:2371–2375

    Article  PubMed  CAS  Google Scholar 

  19. Sairam VK, Kalia A, Rajaraman S, Travis LB (2002) Secondary resistance to cyclosporine A in children with nephrotic syndrome. Pediatr Nephrol 17:842–846

    Article  PubMed  Google Scholar 

  20. Sellier-Leclerc AL, Baudouin V, Kwon T, Macher MA, Guérin V, Lapillonne H, Deschênes G, Ulinski T (2012) Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood—follow-up after CD19 recovery. Nephrol Dial Transplant 27:1083–1089

    Article  PubMed  CAS  Google Scholar 

  21. Ulinski T, Dubourg L, Said MH, Parchoux B, Ranchin B, Cochat P (2005) Switch from cyclosporine A to mycophenolate mofetil in nephrotic children. Pediatr Nephrol 20:482–485

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-ku, Saitama City, Saitama, 339 8551, Japan

    Shuichiro Fujinaga, Tsuneki Watanabe & Akira Ito

  2. Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan

    Tomonosuke Someya & Toshiaki Shimizu

  3. Department of Pediatrics, Juntendo Nerima Hospital, Tokyo, Japan

    Yoshiyuki Ohtomo

  4. Department of Pediatrics, Kansai Medical University, Hirakata, Japan

    Kazunari Kaneko

Authors
  1. Shuichiro Fujinaga
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  2. Tomonosuke Someya
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  3. Tsuneki Watanabe
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  4. Akira Ito
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  5. Yoshiyuki Ohtomo
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  6. Toshiaki Shimizu
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  7. Kazunari Kaneko
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Correspondence to Shuichiro Fujinaga.

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Fujinaga, S., Someya, T., Watanabe, T. et al. Cyclosporine versus mycophenolate mofetil for maintenance of remission of steroid-dependent nephrotic syndrome after a single infusion of rituximab. Eur J Pediatr 172, 513–518 (2013). https://doi.org/10.1007/s00431-012-1913-3

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  • DOI: https://doi.org/10.1007/s00431-012-1913-3

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