Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
권호 표지
DOI QR코드

DOI QR Code

Efficacy and Safety of Mycophenolate Mofetil in Children with Steroid Dependent Nephrotic Syndrome

  • Lim, Taek Jin (Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Kim, Seong Heon (Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Kim, Su Young (Department of Pediatrics, Pusan National University Children's Hospital)
  • Received : 2015.09.20
  • Accepted : 2015.10.25
  • Published : 2015.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Steroid dependent nephrotic syndrome (SDNS) is a chronic illness in childhood hard to treat. Steroid sparing drugs are often used, because long-term steroid therapy can cause severe side effects. We studied to compare efficacy between MMF and other drugs including cyclosporine and levamisole. Methods: This study was performed retrospectively on patients with SDNS, who were treated at Pusan National University Children's hospital. MMF group included 11 patients who were treated with MMF for at least six months between June 2012 and July 2014. As control groups, cyclosporine group (n=15) and levamisole group (n=18) included patients treated between January 2008 and July 2014. Number of relapse was analyzed in patients treated more than six months, and relapse free for one year was analyzed in patients treated more than one year. Results: In MMF group, ten were boys and mean age at onset was 5.8 years. Mean age at starting of MMF was 8.6 years. Number of relapse in MMF group was reduced significantly after treatment from 3.4 /year to 0.2 /year (P=0.003). There was no significant difference in number of relapse among groups (MMF: 0.2 /year, cyclosporine: 0.5 /year, levamisole: 0.5 /year). Comparing the early relapse within six months after treatment levamisole group was significantly higher than the other two groups (P=0.04). Conclusions: MMF which is used in SDNS significantly reduced the relapse and side effects were rare. In addition, MMF did not show any significant difference in comparison with the other two groups in number of relapse and relapse free for one year.

Keywords

References

  1. Primary nephrotic syndrome in children: Clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A report of the international study of kidney disease in children. Kidney Int 1981;20:765-71. https://doi.org/10.1038/ki.1981.209
  2. Cheong WY. Recent advance in nephrotic syndrome. J Korean Soc Pediatr Nephrol 2002;6:15-24.
  3. Siegel NJ, Goldberg B, Krassner LS, Hayslett JP. Long-term follow-up of children with steroid-responsive nephrotic syndrome. J Pediatr 1972;81:251-8. https://doi.org/10.1016/S0022-3476(72)80291-9
  4. Hoyer PF, Krull F, Brodehl J. Cyclosporin in frequently relapsing minimal change nephrotic syndrome. Lancet 1986;2:335.
  5. Tanphaichitr P, Tanphaichitr D, Sureeratanan J, Chatasingh S. Treatment of nephrotic syndrome with levamisole. J Pediatr 1980;96:490-3. https://doi.org/10.1016/S0022-3476(80)80707-4
  6. Moudgil A, Bagga A, Jordan SC. Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: Current status and future directions. Pediatr Nephrol 2005;20:1376-81. https://doi.org/10.1007/s00467-005-1964-z
  7. Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, et al. Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: A multicentre randomized controlled trial. Nephrol Dial Transplant 1993;8:1326-32.
  8. Inoue Y, Iijima K, Nakamura H, Yoshikawa N. Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 1999;13:33-8. https://doi.org/10.1007/s004670050558
  9. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. north america nephrotic syndrome study group. Kidney Int 1999;56:2220-6. https://doi.org/10.1046/j.1523-1755.1999.00778.x
  10. Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, et al. Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 2010;25:3956-62. https://doi.org/10.1093/ndt/gfq318
  11. Tanaka R, Yoshikawa N, Kitano Y, Ito H, Nakamura H. Long-term ciclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 1993;7:249-52. https://doi.org/10.1007/BF00853209
  12. Hino S, Takemura T, Okada M, Murakami K, Yagi K, Fukushima K, et al. Follow-up study of children with nephrotic syndrome treated with a long-term moderate dose of cyclosporine. Am J Kidney Dis 1998;31:932-9. https://doi.org/10.1053/ajkd.1998.v31.pm9631836
  13. Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y. Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 2006;91:666-70. https://doi.org/10.1136/adc.2005.080960
  14. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, et al. Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 2002;61:1801-5. https://doi.org/10.1046/j.1523-1755.2002.00303.x
  15. Nakamura T, Nozu K, Iijima K, Yoshikawa N, Moriya Y, Yamamori M, et al. Association of cumulative cyclosporine dose with its irreversible nephrotoxicity in japanese patients with pediatriconset autoimmune diseases. Biol Pharm Bull 2007;30:2371-5. https://doi.org/10.1248/bpb.30.2371
  16. Sairam VK, Kalia A, Rajaraman S, Travis LB. Secondary resistance to cyclosporin A in children with nephrotic syndrome. Pediatr Nephrol 2002;17:842-6. https://doi.org/10.1007/s00467-002-0896-0
  17. Habashy D, Hodson E, Craig J. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev 2004;(2):CD003594.
  18. Niaudet P, Habib R, Tete MJ, Hinglais N, Broyer M. Cyclosporin in the treatment of idiopathic nephrotic syndrome in children. Pediatr Nephrol 1987;1:566-73. https://doi.org/10.1007/BF00853590
  19. Han JH, Lee KJ, Lee YM, Kim JH, Kim PK. The effect of levamisole in steroid-dependent nephrotic syndrome in children. J Korean Soc Pediatr Nephrol 2001;5:109-16.
  20. Bagga A, Sharma A, Srivastava RN. Levamisole therapy in corticosteroid-dependent nephrotic syndrome. Pediatr Nephrol 1997;11:415-7. https://doi.org/10.1007/s004670050307
  21. Neuhaus TJ, Fay J, Dillon MJ, Trompeter RS, Barratt TM. Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome. Arch Dis Child 1994;71:522-6. https://doi.org/10.1136/adc.71.6.522
  22. Lim HS, Noh US, Choe BH, Koh CW, Koo JH. Therapeutic effects of cytotoxic agents (cyclophosphamide and chlorambucil), cyclosporine and levamisole in children with steroid-dependent nephrotic syndrome. Korean J Nephrol 1997;16:246-53.
  23. Dayal U, Dayal AK, Shastry JC, Raghupathy P. Use of levamisole in maintaining remission in steroid-sensitive nephrotic syndrome in children. Nephron 1994;66:408-12. https://doi.org/10.1159/000187855
  24. Niaudet P, Drachman R, Gagnadoux MF, Broyer M. Treatment of idiopathic nephrotic syndrome with levamisole. Acta Paediatr Scand 1984;73:637-41. https://doi.org/10.1111/j.1651-2227.1984.tb09988.x
  25. Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. british association for paediatric nephrology. Lancet 1991;337:1555-7. https://doi.org/10.1016/0140-6736(91)93257-A
  26. Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G. Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 2003;18:772-7. https://doi.org/10.1007/s00467-003-1174-5
  27. Chandra M, Susin M, Abitbol C. Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil. Pediatr Nephrol 2000;14:224-6. https://doi.org/10.1007/s004670050047
  28. Bagga A, Hari P, Moudgil A, Jordan SC. Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 2003;42:1114-20. https://doi.org/10.1053/j.ajkd.2003.08.011
  29. Gellermann J, Querfeld U. Frequently relapsing nephrotic syndrome: Treatment with mycophenolate mofetil. Pediatr Nephrol 2004;19:101-4. https://doi.org/10.1007/s00467-003-1300-4
  30. Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB. Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 2003;18:833-7. https://doi.org/10.1007/s00467-003-1175-4
  31. Ulinski T, Dubourg L, Said MH, Parchoux B, Ranchin B, Cochat P. Switch from cyclosporine A to mycophenolate mofetil in nephrotic children. Pediatr Nephrol 2005;20:482-5. https://doi.org/10.1007/s00467-004-1778-4
  32. Zhao M, Chen X, Chen Y, Liu Z, Liu Y, Lu F, et al. Clinical observations of mycophenolate mofetil therapy in refractory primary nephrotic syndrome. Nephrology (Carlton) 2003;8:105-9. https://doi.org/10.1046/j.1440-1797.2003.00146.x
  33. Banerjee S, Pahari A, Sengupta J, Patnaik SK. Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil. Pediatr Nephrol 2013;28:93-7. https://doi.org/10.1007/s00467-012-2278-6
  34. Mendizabal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J. Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome. Pediatr Nephrol 2005;20:914-9. https://doi.org/10.1007/s00467-005-1877-x
  35. Gellermann J, Weber L, Pape L, Tonshoff B, Hoyer P, Querfeld U, et al. Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 2013;24:1689-97. https://doi.org/10.1681/ASN.2012121200