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Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO

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Abstract

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on glomerulonephritis (GN) is intended to assist the practitioner caring for patients with GN. Two chapters of this guideline focus specifically on nephrotic syndrome in children. Guideline development followed a thorough evidence review, and management recommendations and suggestions were based on the best available evidence. Critical appraisal of the quality of evidence and strength of recommendations followed the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach. Chapters 3 and 4 of the guideline focus on the management of nephrotic syndrome in children aged 1–18 years. Guideline recommendations for children who have steroid-sensitive nephrotic syndrome (SNSS), defined by their response to corticosteroid therapy with complete remission, are addressed here. Recommendations for those with steroid-resistant nephrotic syndrome (SRNS) (i.e., do not achieve complete remission) are discussed in the companion article. Limitations of the evidence, including the paucity of large-scale randomized controlled trials, are discussed. This article provides a short description of the KDIGO process, the guideline recommendations for treatment of SSNS in children and a brief review of relevant treatment trials related to each recommendation.

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Notes

  1. Prednisone and prednisolone are equivalent, used in the same dosage, and have both been used in RCTs. All later references to prednisone or oral corticosteroids refer to prednisone or prednisolone.

References

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

    Article  PubMed  CAS  Google Scholar 

  2. 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. A Report of the International Study of Kidney Disease in Children. Kidney Int 20:765–771

  3. Bagga A, Ali U, Banerjee S, Kanitkar M, Phadke KD, Senguttuvan P, Sethi S, Shah M (2008) Management of steroid-sensitive nephrotic syndrome: revised guidelines. Indian Pediatr 45:203–214

    PubMed  Google Scholar 

  4. 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

    Article  PubMed  Google Scholar 

  5. Haute Autorité de Santé (2008) Syndrome néphrotique idiopathique de l’enfant. Service des affections de longue durée et accords conventionnels:1–22

  6. 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 70:2058–2065

    PubMed  CAS  Google Scholar 

  7. Lombel RM, Hodson E, Gipson D (2012) Treatment of steroid-resistant nephrotic syndrome in children– new guidelines from KDIGO. Pediatr Nephrol. doi:10.1007/s00467-012-2304-8

  8. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group (2012) KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int, Suppl 2:139–274

  9. Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A, Schunemann HJ (2008) Going from evidence to recommendations. BMJ 336:1049–1051

    Article  PubMed  Google Scholar 

  10. Hodson EM, Willis NS, Craig JC (2007) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev:CD001533

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

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  13. Feber J, Al-Matrafi J, Farhadi E, Vaillancourt R, Wolfish N (2009) Prednisone dosing per body weight or body surface area in children with nephrotic syndrome: is it equivalent? Pediatr Nephrol 24:1027–1031

    Article  PubMed  Google Scholar 

  14. Saadeh S, Baracco R, Jain A, Kapur G, Mattoo TK, Valentini R (2011) Weight or body surface area dosing of steroids in nephrotic syndrome: is there an outcome difference? Pediatr Nephrol 26:2167–2171

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (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

    PubMed  CAS  Google Scholar 

  17. Abeyagunawardena AS, Trompeter RS (2008) Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial. Arch Dis Child 93:226–228

    Article  PubMed  CAS  Google Scholar 

  18. Gulati A, Sinha A, Sreenivas V, Math A, Hari P, Bagga A (2011) Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol 6:63–69

    Article  PubMed  CAS  Google Scholar 

  19. Mattoo 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  CAS  Google Scholar 

  20. Elzouki AY, Jaiswal OP (1988) Long-term, small-dose prednisone therapy in frequently relapsing nephrotic syndrome of childhood. Effect on remission, statural growth, obesity, and infection rate. Clin Pediatr (Phila) 27:387–392

    Article  CAS  Google Scholar 

  21. Srivastava RN, Vasudev AS, Bagga A, Sunderam KR (1992) Long-term, low-dose prednisolone therapy in frequently relapsing nephrotic syndrome. Pediatr Nephrol 6:247–250

    Article  PubMed  CAS  Google Scholar 

  22. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454

    Google Scholar 

  23. Hodson EM, Willis NS, Craig JC (2008) Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev:CD002290

  24. 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  PubMed  CAS  Google Scholar 

  25. Miller DG (1971) Alkylating agents and human spermatogenesis. JAMA 217:1662–1665

    Article  PubMed  CAS  Google Scholar 

  26. Wetzels JF (2004) Cyclophosphamide-induced gonadal toxicity: a treatment dilemma in patients with lupus nephritis? Neth J Med 62:347–352

    PubMed  CAS  Google Scholar 

  27. Williams SA, Makker SP, Ingelfinger JR, Grupe WE (1980) Long-term evaluation of chlorambucil plus prednisone in the idiopathic nephrotic syndrome of childhood. N Engl J Med 302:929–933

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  29. Abeyagunawardena AS, Trompeter RS (2006) Intravenous pulsed versus oral cyclophosphamide therapy in steroid dependant nephrotic syndrome. Pediatr Nephrol 21:1535

    Google Scholar 

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

    Google Scholar 

  31. Fu LS, Shien CY, Chi CS (2004) Levamisole in steroid-sensitive nephrotic syndrome children with frequent relapses and/or steroid dependency: comparison of daily and every-other-day usage. Nephron Clin Pract 97:c137–c141

    Article  PubMed  CAS  Google Scholar 

  32. Hafeez F, Ahmed TM, Samina U (2006) Levamisole in steroid-dependent and frequently relapsing nephrotic syndrome. J Coll Physicians Surg Pak 16:35–37

    PubMed  Google Scholar 

  33. Kemper MJ, Amon O, Timmermann K, Altrogge H, Muller-Wiefel DE (1998) The treatment with levamisole of frequently recurring steroid-sensitive idiopathic nephrotic syndrome in children. Dtsch Med Wochenschr 123:239–243

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  35. Gruppen MP, Bouts AH, Davin JC (2011) The levamisole study in steroid-sensitive idiopathic nephrotic syndrome (SSINS). Pediatr Nephrol 26:1682

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R, Lama G, Zacchello G, Confalonieri R, Altieri P, Bettinelli A, Maschio G, Cinotti GA, Fuiano G, Schena FP, Castellani A, Delia 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

    PubMed  CAS  Google Scholar 

  38. El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M (2005) Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience. Nephrol Dial Transplant 20:2433–2438

    Article  PubMed  CAS  Google Scholar 

  39. Hulton SA, Neuhaus TJ, Dillon MJ, Barratt TM (1994) Long-term cyclosporin A treatment of minimal-change nephrotic syndrome of childhood. Pediatr Nephrol 8:401–403

    Article  PubMed  CAS  Google Scholar 

  40. Niaudet P, Broyer M, Habib R (1991) Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. Clin Nephrol 35(Suppl 1):S31–S36

    PubMed  Google Scholar 

  41. Sinha MD, MacLeod R, Rigby E, Clark AG (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant 21:1848–1854

    Article  PubMed  CAS  Google Scholar 

  42. Wang W, Xia Y, Mao J, Chen Y, Wang D, Shen H, Fu H, Du L, Liu A (2012) Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome. Pediatr Nephrol. doi:10.1007/s00467-012-2228-3

  43. Dotsch J, Dittrich K, Plank C, Rascher W (2006) Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A? Nephrol Dial Transplant 21:1761–1763

    Article  PubMed  Google Scholar 

  44. Morgan C, Sis B, Pinsk M, Yiu V (2011) Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome. Nephrol Dial Transplant 26:2860–2865

    Article  PubMed  CAS  Google Scholar 

  45. Heisel O, Heisel R, Balshaw R, Keown P (2004) New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant 4:583–595

    Article  PubMed  Google Scholar 

  46. El-Husseini A, El-Basuony F, Mahmoud I, Donia A, Sheashaa H, Sabry A, Hassan N, Sayed-Ahmad N, Sobh M (2006) Impact of the cyclosporine-ketoconazole interaction in children with steroid-dependent idiopathic nephrotic syndrome. Eur J Clin Pharmacol 62:3–8

    Article  PubMed  CAS  Google Scholar 

  47. Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805

    Article  PubMed  Google Scholar 

  48. Ishikura K, Ikeda M, Hattori S, Yoshikawa N, Sasaki S, Iijima K, Nakanishi K, Yata N, Honda M (2008) Effective and safe treatment with cyclosporine in nephrotic children: a prospective, randomized multicenter trial. Kidney Int 73:1167–1173

    Article  PubMed  CAS  Google Scholar 

  49. Filler G (2005) How should microemulsified cyclosporine A (Neoral) therapy in patients with nephrotic syndrome be monitored? Nephrol Dial Transplant 20:1032–1034

    Article  PubMed  CAS  Google Scholar 

  50. 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 

  51. Gellerman J, Ouerfeld U (2011) Frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) in children and adolescents: treatment with mycophenolate mofetil (MMF) vs. cyclosporine (CsA). Pediatr Nephrol 26:1579

    Google Scholar 

  52. 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 

  53. Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM (2011) Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol 6:1308–1315

    Article  PubMed  CAS  Google Scholar 

  54. Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279

    Article  PubMed  Google Scholar 

  55. 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 25:461–468

    Article  PubMed  Google Scholar 

  56. Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschenes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  58. Donia A, Ammar HM, El Agroudy A, Moustafa F, Sobh M (2005) Long-term results of two unconventional agents in steroid-dependent nephrotic syndrome. Pediatr Nephrol 20:1420–1425

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA

    Rebecca M. Lombel & Debbie S. Gipson

  2. Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, USA

    Debbie S. Gipson

  3. Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia

    Elisabeth M. Hodson

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

    Elisabeth M. Hodson

  5. Pediatric Nephrology, C.S. Mott Children’s Hospital, 1540 E. Hospital Drive, SPC 4297, Ann Arbor, MI, 48109-4297, USA

    Rebecca M. Lombel

Authors
  1. Rebecca M. Lombel
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  2. Debbie S. Gipson
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  3. Elisabeth M. Hodson
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Correspondence to Rebecca M. Lombel.

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1) Answer: E

2) Answer: C

3) Answer: E

4) Answer: A

5) Answer: E

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Lombel, R.M., Gipson, D.S. & Hodson, E.M. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28, 415–426 (2013). https://doi.org/10.1007/s00467-012-2310-x

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  • DOI: https://doi.org/10.1007/s00467-012-2310-x

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