Pediatric Nephrology

, Volume 28, Issue 3, pp 409–414 | Cite as

Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO

  • Rebecca M. Lombel
  • Elisabeth M. Hodson
  • Debbie S. Gipson
Educational Review


Kidney Disease: Improving Global Outcomes (KDIGO) recently published the clinical practice guideline on glomerulonephritis (GN) to assist the practitioner caring for patients with GN. Chapter 4 of the guideline focuses on managing children aged 1–18 years with steroid-resistant nephrotic syndrome (SRNS), defined by an inability to achieve complete remission with corticosteroid therapy. Guideline development followed a thorough evidence review, and management recommendations and suggestions were based on the best available evidence. Limitations of the evidence, including the paucity of large-scale randomized controlled trials, are discussed. This article provides both the guideline recommendations and a brief review of relevant treatment trials related to each recommendation. This précis serves as a summary of the complete guidelines recently published.


Clinical practice guidelines Steroid-resistant nephrotic syndrome Children Management 



  1. 1.
    McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM (2001) Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol 16:1040–1044PubMedCrossRefGoogle Scholar
  2. 2.
    Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group (2012) KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Inter Suppl 2:139–274Google Scholar
  3. 3.
    Uhlig K, Macleod A, Craig J, Lau J, Levey AS, Levin A, Moist L, Steinberg E, Walker R, Wanner C, Lameire N, Eknoyan G (2006) Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 70:2058–2065PubMedGoogle Scholar
  4. 4.
    Lombel RM, Hodson E, Gipson D (2012) Treatment of steroid sensitive nephrotic syndrome in children–new guidelines from KDIGO. Pediatr Nephrol. doi: 10.1007/s00467-012-2310-x
  5. 5.
    Abrantes MM, Cardoso LS, Lima EM, Penido Silva JM, Diniz JS, Bambirra EA, Oliveira EA (2006) Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis. Pediatr Nephrol 21:1003–1012PubMedCrossRefGoogle Scholar
  6. 6.
    Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, Gibson K, Thomas DB (2006) Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol 21:344–349PubMedCrossRefGoogle Scholar
  7. 7.
    Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC (2005) Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J Am Soc Nephrol 16:1061–1068PubMedCrossRefGoogle Scholar
  8. 8.
    International Study of Kidney Desease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564Google Scholar
  9. 9.
    International Study of Kidney Desease in Children (1974) Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International Study of Kidney Disease in Children. Lancet 2:423–427Google Scholar
  10. 10.
    Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1996) Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children. Pediatr Nephrol 10:590–593PubMedCrossRefGoogle Scholar
  11. 11.
    Chitalia VC, Wells JE, Robson RA, Searle M, Lynn KL (1999) Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. Kidney Int 56:2236–2242PubMedCrossRefGoogle Scholar
  12. 12.
    Cosio FG, Hernandez RA (1996) Favorable prognostic significance of raised serum C3 concentration in patients with idiopathic focal glomerulosclerosis. Clin Nephrol 45:146–152PubMedGoogle Scholar
  13. 13.
    Chernin G, Heeringa SF, Gbadegesin R, Liu J, Hinkes BG, Vlangos CN, Vega-Warner V, Hildebrandt F (2008) Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 23:1455–1460PubMedCrossRefGoogle Scholar
  14. 14.
    Karle SM, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A (2002) Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol 13:388–393PubMedGoogle Scholar
  15. 15.
    Garin EH, Orak JK, Hiott KL, Sutherland SE (1988) Cyclosporine therapy for steroid-resistant nephrotic syndrome. A controlled study. Am J Dis Child 142:985–988PubMedGoogle Scholar
  16. 16.
    Hodson EM, Willis NS, Craig JC (2010) Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev:CD003594Google Scholar
  17. 17.
    Lieberman KV, Tejani A (1996) A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. J Am Soc Nephrol 7:56–63PubMedGoogle Scholar
  18. 18.
    Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Rivolta E, Rinaldi S, Ghio L, Lusvarghi E, Gusmano R, Locatelli F, Pasquali S, Castellani A, Casa-Alberighi AD (1993) A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int 43:1377–1384PubMedCrossRefGoogle Scholar
  19. 19.
    Gellermann J, Stefanidis CJ, Mitsioni A, Querfeld U (2010) Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations. Pediatr Nephrol 25:1285–1289PubMedCrossRefGoogle Scholar
  20. 20.
    Malina M, Cinek O, Janda J, Seeman T (2009) Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr Nephrol 24:2051–2053PubMedCrossRefGoogle Scholar
  21. 21.
    Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15:722–732PubMedCrossRefGoogle Scholar
  22. 22.
    Caridi G, Perfumo F, Ghiggeri GM (2005) NPHS2 (Podocin) mutations in nephrotic syndrome. Clinical spectrum and fine mechanisms. Pediatr Res 57:54R–61RPubMedCrossRefGoogle Scholar
  23. 23.
    Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A (2009) Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis 53:760–769PubMedCrossRefGoogle Scholar
  24. 24.
    Bagga A, Mudigoudar BD, Hari P, Vasudev V (2004) Enalapril dosage in steroid-resistant nephrotic syndrome. Pediatr Nephrol 19:45–50PubMedCrossRefGoogle Scholar
  25. 25.
    Li Z, Duan C, He J, Wu T, Xun M, Zhang Y, Yin Y (2010) Mycophenolate mofetil therapy for children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 25:883–888PubMedCrossRefGoogle Scholar
  26. 26.
    Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Hogan SL, Middleton JP, Vehaskari VM, Flynn PA, Powell LM, Vento SM, McMahan JL, Siegel N, D’Agati VD, Friedman AL (2011) Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 80:868–878PubMedCrossRefGoogle Scholar
  27. 27.
    de Mello VR, Rodrigues MT, Mastrocinque TH, Martins SP, de Andrade OV, Guidoni EB, Scheffer DK, Martini Filho D, Toporovski J, Benini V (2010) Mycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome. Pediatr Nephrol 25:453–460PubMedCrossRefGoogle Scholar
  28. 28.
    Hari P, Bagga A, Mantan M (2004) Short term efficacy of intravenous dexamethasone and methylprednisolone therapy in steroid resistant nephrotic syndrome. Indian Pediatr 41:993–1000PubMedGoogle Scholar
  29. 29.
    Ehrich JH, Geerlings C, Zivicnjak M, Franke D, Geerlings H, Gellermann J (2007) Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 22:2183–2193PubMedCrossRefGoogle Scholar
  30. 30.
    Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282PubMedCrossRefGoogle Scholar
  31. 31.
    Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschenes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755PubMedCrossRefGoogle Scholar
  32. 32.
    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 5:2207–2212PubMedCrossRefGoogle Scholar
  33. 33.
    Prytula A, Iijima K, Kamei K, Geary D, Gottlich E, Majeed A, Taylor M, Marks SD, Tuchman S, Camilla R, Ognjanovic M, Filler G, Smith G, Tullus K (2010) Rituximab in refractory nephrotic syndrome. Pediatr Nephrol 25:461–468PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  • Rebecca M. Lombel
    • 1
    • 5
  • Elisabeth M. Hodson
    • 2
    • 3
  • Debbie S. Gipson
    • 1
    • 4
  1. 1.Division of Nephrology, Department of Pediatrics and Communicable DiseasesUniversity of MichiganAnn ArborUSA
  2. 2.Centre for Kidney ResearchThe Children’s Hospital at WestmeadWestmead, SydneyAustralia
  3. 3.Sydney School of Public HealthUniversity of SydneySydneyAustralia
  4. 4.Michigan Institute for Clinical and Health ResearchUniversity of MichiganAnn ArborUSA
  5. 5.Pediatric NephrologyC.S. Mott Children’s HospitalAnn ArborUSA

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