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A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome

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Abstract

Cyclosporine A (CsA) has relieved children with steroid-dependent nephrotic syndrome (NS) from steroid toxicity. However, most patients frequently relapse again when CsA is withdrawn, resulting in the development of CsA nephropathy for its long-term use. In order to assess the efficacy of mycophenolate mofetil (MMF) therapy, we prospectively analyzed 12 children with idiopathic steroid-dependent NS requiring long-term CsA therapy with MMF for at least 6 months. Mean follow-up after starting MMF was 11 months (range 6–42). The mean MMF dose required was 610±95 mg/m2/12 h, which maintained mean predose mycophenolic acid (C0-MPA) levels of 2.4±1.1 mcg/ml. Treatment with MMF resulted in CsA and/or prednisolone (PSL) sparing, with a reduction in mean CsA dose from 3.5±1.3 to 1.5±2.4 mg/kg/day (p<0.01), and mean PSL dose from 0.29±0.16 to 0.21±0.11 mg/kg/day (p<0.05). Nine of 12 patients (75%) were finally able to be weaned off CsA. Mean relapse rates decreased from 2.7±1.6 to 0.6±0.9 episodes/year (p<0.01). Relapse-free ratio on MMF therapy was lower in patients whose average C0-MPA levels were less than 2 mcg/ml (p<0.05). Our experience demonstrates that MMF therapy results in significant CsA and/or steroid sparing and reduction in relapse rates in children with CsA-dependent NS.

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References

  1. Capodicasa G, De Santo NG, Nuzzi F, Giordano C (1986) Cyclosporin A in nephrotic syndrome of children—a 14 month experience. Int Pediatr Nephrol 7:69–72

    CAS  Google Scholar 

  2. Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Riviolta E, Rinaldi S, Ghio L, Lusvarghi E, Gusmano R, Locatelli F, Pasquali S, Castellani A, Della Csa-Alberighi O (1993) A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int 43:1377–1384

    Article  CAS  PubMed  Google Scholar 

  3. Niaudet P, Habib R (1994) Cyclosporine in the treatment of idiopathic nephrosis. J Am Soc Nephrol 5:1049–1056

    CAS  PubMed  Google Scholar 

  4. Chan TM, Li FK, Tang CSO, Wong RWS, Fang GX, Ji YL, Lau CS, Wong AKM, Tong MKL, Chan KW, Lai KN (2000) Efficacy of mycofenolate mofetil in patients with diffuse proliferative lupus nephritis. N Eng J Med 343:1156–1162

    Article  CAS  Google Scholar 

  5. Lau KK, Jones DP, Hastings MC, Gaber LW, Ault BH (2006) Short-term outcomes of severe lupus nephritis in a cohort of predominantly African-American children. Pediatr Nephrol 21:655–662

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Mendizalbal 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  Google Scholar 

  8. 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 

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

    Article  CAS  PubMed  Google Scholar 

  10. 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 

  11. Novak I, Frank R, Vento S, Vergara M, Gauthier B, Trachtman H (2005) Efficacy of mycophenolate mofetil in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol 20:1265–1268

    Article  PubMed  Google Scholar 

  12. Borrows R, Chusney G, Loucaidou M, James A, Lee J, Tromp JV, Owen J, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D (2006) Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity. Am J Transplant 6:121–128

    Article  CAS  PubMed  Google Scholar 

  13. Ohtomo Y, Fujinaga S, Takada M, Murakami H, Akashi S, Shimizu T, Kaneko K, Yamashiro Y (2005) High-dose mizoribine therapy for childhood-onset frequently relapsing steroid-dependent nephrotic syndrome with cyclosporin nephrotoxicity. Pediatr Nephrol 20:1744–1749

    Article  PubMed  Google Scholar 

  14. International Study of Kidney Disease in Children (1981) Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. Kidney Int 20:765–771

    Article  Google Scholar 

  15. International Study of Kidney Disease in Children (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. J Pediatr 101:514–518

    Article  Google Scholar 

  16. Langman LJ, Legatt DF, Halloran PF, Yatscoff RW (1996) Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression in renal transplant recipients. Transplantation 62:666–672

    Article  CAS  PubMed  Google Scholar 

  17. 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  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kemper MJ, Altrogge H, Ludwig K, Timmermann K, Muller-Wiefel DE (2000) Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 14:772–775

    Article  CAS  PubMed  Google Scholar 

  19. Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1996) Cyclophosphamide does not benefit patients with focal segmental glomeruloscrelosis. A report of the International Study of Kidney Disease in Children. Pediatr Nephrol 10:590–593

    Article  CAS  PubMed  Google Scholar 

  20. Moudgil A, Bagga A, Jordan SC (2005) Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions. Pediatr Nephrol 20:1376–1381

    Article  PubMed  Google Scholar 

  21. Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T cell function. Lancet ii:556–559

    Article  Google Scholar 

  22. Tredger MJ, Brown NW (2006) Mycophenolate: better value through monitoring? Transplantation 81:507–508

    Article  PubMed  Google Scholar 

  23. Pape L, Froede K, Strehlau J, Ehrich JH, Offner G (2003) Alterations of cyclosporin a metabolism induced by mycophenolate mofetil. Pediatr Transplant 7:302–304

    Article  CAS  PubMed  Google Scholar 

  24. Filler G (2004) Drug interactions between mycophenolate and cyclosporine. Pediatr Transplant 8:201–204

    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, 339 8551, Japan

    Shuichiro Fujinaga & Daisuke Umino

  2. Department of Pediatrics, Juntendo Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 117-8521, Japan

    Yoshiyuki Ohtomo

  3. Department of Pediatrics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Mayako Takemoto, Toshiaki Shimizu & Yuichiro Yamashiro

  4. Department of Pediatrics, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan

    Kazunari Kaneko

Authors
  1. Shuichiro Fujinaga
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  2. Yoshiyuki Ohtomo
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  3. Daisuke Umino
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  4. Mayako Takemoto
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  5. Toshiaki Shimizu
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  6. Yuichiro Yamashiro
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  7. Kazunari Kaneko
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Correspondence to Shuichiro Fujinaga.

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Fujinaga, S., Ohtomo, Y., Umino, D. et al. A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome. Pediatr Nephrol 22, 71–76 (2007). https://doi.org/10.1007/s00467-006-0294-0

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  • DOI: https://doi.org/10.1007/s00467-006-0294-0

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