Skip to main content
SpringerLink
Log in

Evidence-based management of steroid-sensitive nephrotic syndrome

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

An Erratum to this article was published on 04 February 2006

Abstract

Using data from systematic reviews and randomised controlled trials, the evidence for managing steroid sensitive nephrotic syndrome (SSNS) is reviewed. In the initial episode, increased duration (3–7 months) of prednisone compared with 2 months significantly reduced the risk for relapse at 12–24 months [relative risk (RR) 0.70; 95% confidence intervals (CI) 0.58–0.84] without increase in adverse effects. Six months of prednisone was significantly more effective than 3 months (RR 0.57; 95% CI 0.45–0.71). Higher prednisone doses given for the same duration reduced the risk of relapse (RR 0.59; 95% CI 0.42–0.84) suggesting that both dose and duration of prednisone therapy lead to prolonged remission. In relapsing SSNS prolonged prednisone treatment, daily prednisone during infections, oral or intravenous cyclophosphamide, chlorambucil, levamisole and cyclosporin significantly reduced the risk of relapse. Comparative effects of these options remain uncertain because of the absence of head-to-head trials, but existing trial evidence is strongest for cyclophosphamide and cyclosporin. Further adequately powered multinational trials are required to determine the optimum induction dose and duration of prednisone in the initial episode of SSNS and to determine the relative efficacies of immunosuppressive agents and the efficacy of newer agents, including mycophenolate and tacrolimus, in relapsing SSNS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schlesinger ER, Sultz HA, Mosher WE, Feldman JG (1968) The nephrotic syndrome. Its incidence and implications for the community. Am J Dis Child 116:623–632

    CAS  PubMed  Google Scholar 

  2. McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM (2001) Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol 16:1040–1044

    Article  CAS  PubMed  Google Scholar 

  3. International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: Prediction of histology from clinical and laboratory characteristics at time of diagnosis. Kidney Int 13:159–165

    PubMed  Google Scholar 

  4. International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564

    PubMed  Google Scholar 

  5. 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 proliferation. Kidney Int 20:765–771

    PubMed  Google Scholar 

  6. Koskimies O, Vilska J, Rapola J, Hallman N (1982) Long-term outcome of primary nephrotic syndrome. Arch Dis Child 57:544–548

    CAS  PubMed  Google Scholar 

  7. Tarshish P, Tobin JN, Bernstein J, Edelmann CMJ (1997) Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 8:769–776

    CAS  PubMed  Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. Takeda A, Takimoto H, Mizusawa Y, Simoda M (2001) Prediction of subsequent relapse in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 16:888–893

    Article  CAS  PubMed  Google Scholar 

  10. Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux M-F, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grunfeld J-P, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557

    Article  PubMed  Google Scholar 

  11. Arneil GC (1971) The nephrotic syndrome. Pediatr Clin North Am 18:547–559

    CAS  PubMed  Google Scholar 

  12. Anonymous (1979) Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. A report of “Arbeitsgemeinschaft für Pädiatrische Nephrologie”. Lancet 1:401–403

    PubMed  Google Scholar 

  13. Ekka BK, Bagga A, Srivastava RN (1997) Single- versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Pediatr Nephrol 11:597–599

    Article  CAS  PubMed  Google Scholar 

  14. Hodson EM, Knight JF, Willis NS, Craig JC (2005) Corticosteroid therapy for nephrotic syndrome in children. The Cochrane Database of Systematic Reviews Issue 1. Art. no.: CD001533. DOI: 10.1002/14651858.CD001533

  15. Hodson EM, Knight JF, Willis NS, Craig JC (2000) Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomised controlled trials. Arch Dis Child 83:45–51

    Article  CAS  PubMed  Google Scholar 

  16. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1988) Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Lancet 1:380–383

    PubMed  Google Scholar 

  17. Kleinknecht C, Broyer M, Parchoux B, Loirat C, Nivet H, Palcoux JB, Ami-Moussa R (1982) Comparison of short and long treatment at onset of steroid sensitive nephrosis (SSN). Preliminary results of a multicenter controlled trial for the French Society of Pediatric Nephrology. Int J Pediatr Nephrol 3:45

    Google Scholar 

  18. Hiraoka M, Tsukahara H, Haruki S, Hayashi S, Takeda N, Miyagawa K, Okuhara K, Suehiro F, Ohshima Y, Mayumi M for the West Japan Cooperative Study of Kidney Disease in Children (2000) Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome. Kidney Int 58:1247–1252

    Article  CAS  PubMed  Google Scholar 

  19. Pecoraro C, Caropreso MR, Malgieri G, Raddi G, Piscitelli A, Nuzzi F (2004) Therapy of first episode of steroid responsive nephrotic syndrome: a randomised controlled trial. Pediatr Nephrol 19:C72

    Google Scholar 

  20. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1999) Results of the nephrotic syndrome study VIII of the APN: New standard treatment versus new standard treatment plus 8 weeks cyclosporin A. Pediatr Nephrol 13:C26

    Article  Google Scholar 

  21. Yoshikawa N, Ito H, Takehoshi Y, Honda M, Awazu M, Iijima K, Nakamura H, Seino Y, Takeda N, Hattori S, Matsuda I (1998) Standard versus long-term prednisolone with Sairei-to in childhood steroid-responsive nephrotic syndrome: a prospective controlled study. Jpn J Nephrol 40:587–590

    CAS  Google Scholar 

  22. Matoo TK, Mahmoud MA (2000) Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 85:343–345

    Article  PubMed  Google Scholar 

  23. Jayantha UK (2004) Comparison of ISKDC regime with a 7-month steroid regime in the first attack of nephrotic syndrome. Pediatr Nephrol 19:C81

    Google Scholar 

  24. Broyer M, Terzi F, Lehnert A, Gagnadoux MF, Guest G, Niaudet P (1997) A controlled study of deflazacort in the treatment of idiopathic nephrotic syndrome. Pediatr Nephrol 11:418–422

    Article  CAS  PubMed  Google Scholar 

  25. Imbasciati E, Gusmano R, Edefonti A, Zucchelli P, Pozzi C, Grassi C, Della Volpe M, Performo F, Petrone P, Picca M, Claris Appiani A, Pasquali S, Ponticelli (1985) Controlled trial of methylprednisolone pulses and low dose oral prednisone for the minimal change nephrotic syndrome. BMJ 291:1305–1308

    Google Scholar 

  26. Durkan AM, Hodson EM, Willis NS, Craig JC (2001) Immunosuppressive agents in childhood nephrotic syndrome: a meta-analysis of randomised controlled trials. Kidney Int 59:1919–1927

    Article  CAS  PubMed  Google Scholar 

  27. Durkan A, Hodson EM, Willis NS, Craig JC (2001) Non-corticosteroid treatment for nephrotic syndrome in children. The Cochrane Database of Systematic Reviews Issue 4. Art. no.: CD002290. DOI: 10.1002/14651858.CD002290

  28. Anonymous (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Eng J Med 306:451–454

    Google Scholar 

  29. Ueda N, Kuno K, Ito S (1990) Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Arch Dis Child 65:1147–1150

    CAS  PubMed  Google Scholar 

  30. Anonymous (1987) Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child 62:1102–1106

    PubMed  Google Scholar 

  31. Prasad N, Gulati S, Sharma RK, Singh U, Ahmed M (2004) Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephol 19:494–498

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zachello G, Confalonieri R, Altieri P, Bettinelli A, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Della Casa-Alberighi O (1993) Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 8:1326–1332

    Google Scholar 

  34. Niaudet P and the French Society of Paediatric Nephology (1992) Comparison of cyclosporin and chlorambucil in the treatment of steroid-dependent idiopathic nephrotic syndrome: A multicentre randomized controlled trial. Pediatr Nephrol 6:1–3

    Article  CAS  PubMed  Google Scholar 

  35. El-Husseini A, El-Basuony F, Mahmoud I, Donia A, Hassan N, Sayd-Ahmad N, Sobh M (2004) Co-administration of cyclosporine and ketoconazole in idiopathic childhood nephrosis. Pediatr Nephrol 19:976–981

    Article  PubMed  Google Scholar 

  36. Weiss R (1993) Randomized double-blind placebo controlled trial of levamisole for children with frequently relapsing/steroid dependent nephrotic syndrome. J Am Soc Nephrol 4:289

    Google Scholar 

  37. British Association for Paediatric Nephrology (1991) Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. Lancet 337:1555–1557

    PubMed  Google Scholar 

  38. Rashid HU, Ahmed S, Fatima N, Khanam A (1996) Levamisole in the treatment of steroid dependent or frequent relapsing nephrotic syndrome in children. Bangladesh Renal J 15:6–8

    Google Scholar 

  39. Alsaran K, Grisaru S, Stephens D, Arbus G (2001) Levamisole vs. cyclophosphamide for frequently-relapsing steroid-dependent nephrotic syndrome. Clin Nephrol 56:289–294

    CAS  PubMed  Google Scholar 

  40. Palcoux JB, Niaudet P, Goumy P (1994) Side effects of levamisole in children with nephrosis. Pediatr Nephrol 8:263–264

    Article  CAS  Google Scholar 

  41. Barbano G, Ginevri F, Ghiggeri GM, Gusmano R (1999) Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. Pediatr Nephrol 13:602–603

    Article  CAS  PubMed  Google Scholar 

  42. Yoshioka K, Ohashi Y, Sakai T, Ito H, Yoshikawa N, Nakamura H, Tanizawa T, Wada H, Maki S for the Pediatric Mizoribine Study Group in Japan (2000) A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome. Kidney Int 58:317–324

    Article  CAS  PubMed  Google Scholar 

  43. Rowe PC, McLean RH, Ruley EJ, Salcedo JR, Baumgardner B, Zaugg B, Mellits ED, DeAngelis C (1990) Intravenous immunoglobulin in minimal change nephrotic syndrome: a crossover trial. Pediatr Nephrol 4:32–35

    Article  CAS  PubMed  Google Scholar 

  44. Trompeter RS, Thomson PD, Barratt TM, Soothill JF (1978) Controlled trial of disodium cromoglycate in prevention of relapse of steroid-responsive nephrotic syndrome of childhood. Arch Dis Child 53:430–432

    CAS  PubMed  Google Scholar 

  45. Hogg RJ, Fitzgibbons L, Buick J, Bunke M, Ault B, Baqi N, Trachtman H, Swinford R on behalf of the Southwest Pediatric Nephrology Study Group (2004) Clinical trial of mycophenolate mofetil (MMF) for frequent relapsing nephrotic syndrome in children. Pediatr Nephrol 19:C66

    Article  Google Scholar 

  46. 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 

  47. Sinha MD, Macleod R, Rigby E, Clark AG (2004) Treatment of severe steroid dependent nephrotic syndrome (SDNS) in paediatrics with tacrolimus therapy. Pediatr Nephrol 19:C72

    Google Scholar 

  48. Kausman JY, Yin L, Jones CL, Powell HR (2004) Vincristine in steroid-dependent nephrotic syndrome. Pediatr Nephrol 19:C99

    Google Scholar 

  49. Jayantha UK (2004) Captopril therapy in children with steroid dependent nephrotic syndrome and their long term follow up. Pediatr Nephrol 19:C98

    Google Scholar 

  50. Davin JC, Merkus MP (2005) Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr Nephrol 20:10–14

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This review was presented at the 13th Congress of the International Pediatric Nephrology Association, 29 August to 2 September 2004, Adelaide, Australia.

Author information

Authors and Affiliations

  1. Cochrane Renal Group, NHMRC Centre for Clinical Research Excellence in Renal Medicine, Centre for Kidney Research, The Children’s Hospital at Westmead, Locked Bag 4001, NSW 2145, Westmead, Australia

    Elisabeth M. Hodson, Jonathan C. Craig & Narelle S. Willis

  2. School of Public Health, University of Sydney, Sydney, Australia

    Elisabeth M. Hodson & Jonathan C. Craig

Authors
  1. Elisabeth M. Hodson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan C. Craig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Narelle S. Willis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabeth M. Hodson.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00467-006-2156-1

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hodson, E.M., Craig, J.C. & Willis, N.S. Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20, 1523–1530 (2005). https://doi.org/10.1007/s00467-005-1968-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-005-1968-8

Keywords

Search

Navigation