Treatment approaches in children with steroid sensitive nephrotic syndrome

Year 2011, Volume: 38 Issue: 3, 361 - 367, 01.09.2011

Süleyman Kalman

https://doi.org/10.5798/diclemedj.0921.2011.03.0051

Abstract

Pediatric nephrotic syndrome (NS) is a chronic glomeru­lar disorder, and if untreated, is associated with increased risk of life-threatening infectious, thromboembolism, lipid abnormalities, and malnutrition. The aim of the manage­ment of NS in children is to induce and maintain com­plete remission with resolution of proteinuria and edema without encountering serious adverse effects of therapy. Over 90% of cases in children with idiopathic NS and a majority of them will respond to steroid therapy. However, a substantial number of patients relapse frequently and become steroid dependent. The occurrence of frequent relapses necessitates clear therapeutic strategies in or­der to maintain sustained remission and minimize steroid toxicity. Numerous therapeutic regimens have been pro­posed utilizing steroid sparing agents such as alkylating agents, principally, cyclophosphamide and chlorambucil, calcineurin inhibitors namely cyclosporin A and an immu­nomodulatory drug, levamisole, with variable success and associated side-effects. Recently, mycophenolate mofetil (MMF), tacrolimus, the anti-CD20 antibody, rituximab, have emerged as new therapeutic options for the man­agement of steroid dependent NS in a few uncontrolled clinical trials. It is therefore important that the benefits and risks of these agents are weighed before considering their use in the treatment of patients with NS.

Keywords

Childhood, steroid sensitive nephrotic syn­drome, treatment.

Steroide yanıtlı nefrotik sendromlu çocuklarda tedavi yaklaşımları

Abstract

Çocukluk çağı nefrotik sendromu kronik bir glomerül has­talığıdır. Eğer tedavi edilmezse, yaşamı tehdit eden en­feksiyonlar, tromboembolizm, lipid anormallikleri ve mal­nutrisyon gibi komplikasyonları vardır. Tedavinin amacı proteinüriyi ve ödemi ciddi yan etkiler ortaya çıkmadan düzeltmektir. İdiopatik nefrotik sendromun (İNS) %90\'dan fazlası steroid tedavisine yanıt verir. Bununla birlikte, önemli sayıda hasta sık relaps gösterir ve steroide bağım­lı hale gelir. Sık relapsların ortaya çıkışı remisyon sağla­yıcı ve steroid toksisitesini azaltıcı yeni tedavi stratejilerini gerektirir Steroid yan etkilerinden koruyucu tedavi rejim­leri olarak alkilleyici ajanlar (siklofosfamid ve klorombusil), kalsinörin inhibitörleri (siklosporin A), immunomodulatör ajanlar (levamizol) önerilmiştir. Yakın zamanlarda, mikofe­nolat mofetil (MMF), tacrolimus, anti-CD20 antikoru olan rituximab steroid bağımlı nefrotik sendromda (SBNS) az sayıda kontrolsuz çalışma ile yeni tedavi seçenekleri ola­rak ortaya çıkmıştır. Bu nedenle nefrotik sendromlu ço­cuklarda bu ilaç tedavilerinin, kullanılmadan önce yarar ve risklerinin çok iyi değerlendirilmesinin önemi ortaya çıkmaktadır.

Keywords

Çocukluk çağı, steroide yanıtlı nefro­tik sendrom, tedavi.

References

• Niaudet P, Olivia B. Idiopathic nephrotic syndrome in chil- dren: Clinical aspects. In: Pediatric Nephrology. Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds). Springer-Ve- lag Berlin Heidelberg, 2009; .667-702.
• Hodson EM, Alexander SI, Graf N. Steroid-sensitive neph- rotic syndrome.In: Geary DF, Schaefer F (eds). Compre- hensive Pediatric Nephrology, Mosby Elsevier; Philadel- phia, 2008; 239-256.
• Calışkan S. Nephrotic syndrome. Turkiye Klinikleri J Pediatr Sci 2008;4(1): 67-71.
• Abeyagunewardena AS. Treatment of steroid nephrotic syn- drome. Indian J Pediatr 2005; 72(6): 763-69.
• Krasowska-Kwiecien A, Sancewiz-Pach K, Moczulska A. Idiopathic nephrotic syndrome in Polish children - its vari- ants and associations with HLA. Pediatr Nephrol. 2006; 21(12):1837-46.
• Ruf RG, Lichtenberger A, Karle SM, et al. Arbeitsgemein- schaft Für Pädiatrische Nephrologie Study Group. Patients with mutations in NPHS2 (podocin) do not respond to stan- dard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 2004; 15(3):722-32.
• Ruf RG, Schultheiss M, Lichtenberger A, et al. APN Study Group. Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive neph- rotic syndrome. Kidney Int 2004; 66(2):564-70.
• Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 1974; 2(7880): 556-60.
• Ritz E. Pathogenesis of “idiopathic” nephrotic syndrome. N Engl J Med 1994; 330(1): 61-2.
• Andrew M, Michelson AD, Bovill E, Leaker M, Massicotte MP. Guidelines for antithrombotic therapy in pediatric pa- tients. J Pediatr 1998; 132(4): 575-88.
• Alpay H, Yıldız N, Onar A, Temizer H, Ozcay S. Varicella vaccination in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2002; 17(3): 181-83.
• Hodson EM, Alexander SI. Evaluation and management of steroid-sensitive nephrotic syndrome. Curr Opin Pediatr 2008; 20(2):145-50.
• Abeyagunawardena AS, Sebire NJ, Risdon RA, et al. The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2003;18(9):919-24.
• Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001533.
• Lande MB, Leonard MB. Variability among pediatric neph- rologists in the initial therapy of nephrotic syndrome. Pe- diatr Nephrol 2000; 14(8-9):766-9.
• Kabuki N, Okugawa T, Hayakawa H, Tomizawa S, Kasaha- ra T, Uchiyama M. Influence of age at onset on the outcome of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 1998;12(6):467-70.
• Barrat TM, Clarck G. Minimal change nephrotic syndrome and focal segmental glomerulosclerosis. In: Holiday MA, Barrat TM (eds): Pediatric Nephrology(3th ed.) Williams Wilkins Co, Baltimore, 199; 767-87.
• Kemper MJ, Altrogge H, Ludwig K, Timmermann K, Mül- ler-Wiefel DE. Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 2000; 14(8-9):772-5.
• Vester U, Kranz B, Zimmermann S, Hoyer PF. Cylophos- phamide in steroid-sensitive nephrotic syndrome: outcome and outlook. Pediatr Nephrol 2003; 18(7): 661-4.
• Grupe WE. Chlorambucil in steroid-dependent nephrotic syndrome. J Pediatr 1973;82(4): 598-606.
• Ishikura K, Ikeda M, Hattori S, Yoshikawa N, Sasaki S, Iijima K, Nakanishi K, Yata N, Honda M.Effective and safe treatment with cylosporine in nephrotic children: a prospec- tive, randomized multicenter trial. Kidney Int 2008; 73(10): 1167-73.
• Davin JC,Merkus MP. Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr Nephrol 2005; 20(1): 10-14.
• Afzal K, Bagga A, Menon S, Hari P, Jordan SC. Treatment with mycophenolate mofetil and prednisolone for steroid- dependent nephrotic syndrome. Pediatr Nephrol 2007; 22(12):2059-65.
• Westhoff TH, Schmidt S, Zidek W, Beige J, van der Giet M. Tacrolimus in steroid-resistant and steroid-dependent neph- rotic syndrome. Clin Nephrol 2006; 65(6):393-400.
• Hofstra JM, Deegens JK, Wetzels JF. Rituximab: ef- fective treatment for severe steroid-dependent minimal change nephrotic syndrome? Nephrol Dial Transplant 2007;22(7):2100-2.
• Smith G. Is there a role for rituximab in the treatment of idiopathic childhood nephrotic syndrome? Pediatr Nephrol 2007; 22: 893-98.
• Gulati A, Sinha A, Jordan SC, et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol 2010;5(12):2207-12.
• Ulinski T, Carlier-Legris A, Schlecht D, Ranchin B, Co- chat P. Triamcinoloneacetonide: a new management of noncompliance in nephrotic children. Pediatr Nephrol 2005;20(6):759-62.
• Buemi M, Nostro L, Crascì E, Barillà A, Cosentini V, Aloisi C, Sofi T, Campo S, Frisina N. Statins in nephrotic syn- drome: a new weapon against tissue injury. Med Res Rev 2005 Nov;25(6):587-609.
• Durkan A, Hodson EM, Willis NS, Craig JC. Non-corti- costeroid treatment for nephrotic syndrome in children. Co- chrane Database Syst Rev. 2005; 18: (2):CD002290.
• van Husen M, Kemper MJ. New therapies in steroid-sen- sitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol. 2011 26(6); 881-92.
• Kawasaki Y, Suzuki J, Takahashi A, Isome M, Nozawa R, Suzuki H. Mizoribine oral pulse therapy for steroid-depen- dentnephrotic syndrome. Pediatr Nephrol 2005; 20: 96-98.
• Kausman JY, Yin L, Jones CL, Johnstone L, Powell HR. Vincristine treatment in steroid-dependent nephrotic syn- drome. Pediatr Nephrol 2005; 20:1416–1419.
• Arun S, Bhatnagar S, Menon S, Saini S, Hari P, Bagga A. Efficacy of zinc supplements in reducing relapses in ste- roid-sensitive nephrotic syndrome. Pediatr Nephrol 2009; 24 (8):1583-6.