Skip to main content
Log in

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods

We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3–6) after the onset of MMF treatment. The characteristics of responder patients (n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n = 22) were compared by univariate analysis and multivariate logistic regression.

Results

Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8–30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01).

Conclusions

MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Deschênes G, Leclerc A (2010) Epidemiology of the idiopathic nephrotic syndrome. Arch Pédiatrie Organe Off Sociéte Fr Pédiatrie 17:622–623. 693X(10)70028-2

  2. Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA (2009) Management of childhood onset nephrotic syndrome. Pediatrics 124:747–757. doi:10.1542/peds.2008-1559

    Article  PubMed  Google Scholar 

  3. van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892

    Article  PubMed  Google Scholar 

  4. Büscher AK, Kranz B, Büscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Bröking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol CJASN 5:2075–2084

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Hogg RJ, Fitzgibbons L, Bruick J, Ault B, Baqi N, Trachtman H, Swinford R (2006) Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 1:1173–1178

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Dorresteijn EM, Kist-van Holthe JE, Levtchenko EN, Nauta J, Hop WC, van der Heijden AJ (2008) Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome. Pediatr Nephrol 23:2013–2020

    Article  PubMed  Google Scholar 

  10. Baudouin V, Alberti C, Lapeyraque A-L, Bensman A, André JL, Broux F, Cailliez M, Decramer S, Niaudet P, Deschênes G, Jacqz-Aigrain E, Loirat C (2012) Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial. Pediatr Nephrol 27:389–396

    Article  PubMed  Google Scholar 

  11. Bérard 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. Néphrol Thér 1:150–156

    Article  PubMed  Google Scholar 

  12. (1984) Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 years’ observation. Report of the International Study of Kidney Disease in Children. Pediatrics 73:497–501

  13. Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS (2003) The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 18:919–924

    Article  PubMed  Google Scholar 

  14. Azib S, Macher MA, Kwon T, Dechartres A, Alberti C, Loirat C, Deschênes G, Baudouin V (2011) Cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:927–932

    Article  PubMed  Google Scholar 

  15. Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184

    Article  CAS  PubMed  Google Scholar 

  16. Zagury A, de Oliveira AL, de Moraes CAP, de Araujo Montalvão JA, Novaes RH, de Sá VM, Monteiro de Carvalho Dde B, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920

    Article  PubMed  Google Scholar 

  17. Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282

    Article  CAS  PubMed  Google Scholar 

  18. Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118

    Article  CAS  PubMed  Google Scholar 

  19. Heidt S, Roelen DL, Eijsink C, van Kooten C, Claas FH, Mulder A (2008) Effects of immunosuppressive drugs on purified human B cells: evidence supporting the use of MMF and rapamycin. Transplantation 86:1292–1300

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Gellermann J, Weber L, Pape L, Tönshoff B, Hoyer P, Querfeld U (2013) Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Banerjee S, Pahari A, Sengupta J, Patnaik SK (2013) Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil. Pediatr Nephrol 28:93–97

    Article  PubMed  Google Scholar 

  23. 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 B 20:1265–1268

    Article  Google Scholar 

  24. Kim J, Patnaik N, Chorny N, Frank R, Infante L, Sethna C (2014) Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single-center experience. Nephron Extra 4:8–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Afzal K, Bagga A, Menon S, Hari P, Jordan SC (2007) Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome. Pediatr Nephrol 22:2059–2065

    Article  PubMed  Google Scholar 

  26. Frange P, Frey MA, Deschênes G (2005) Immunity and immunosuppression in childhood idiopathic nephrotic syndrome. Arch Pediatr 12:305–315

    Article  CAS  PubMed  Google Scholar 

  27. Sellier-Leclerc A-L, Macher M-A, Loirat C, Guérin V, Watier H, Peuchmaur M, Baudouin V, Deschênes G (2010) Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 25:1109–1115

    Article  PubMed  Google Scholar 

  28. Gea-Banacloche JC (2010) Rituximab-associated infections. Semin Hematol 47:187–198

    Article  CAS  PubMed  Google Scholar 

  29. Larsen CP, Freedman BI (2015) Apolipoprotein L1-associated nephropathy and the future of renal diagnostics. J Am Soc Nephrol 26:1232–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laurène Dehoux.

Ethics declarations

This work was approved by the local ethics committee.

Conflict of interest

The author(s) declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dehoux, L., Hogan, J., Dossier, C. et al. Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome. Pediatr Nephrol 31, 2095–2101 (2016). https://doi.org/10.1007/s00467-016-3400-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-016-3400-y

Keywords

Navigation