BACKGROUND: Eighty to ninety per cent of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in children who relapse frequently. However these non-corticosteroid agents also have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from proceedings and contact with known investigators. Search date: August 2004 SELECTION CRITERIA: RCTs or quasi-RCTs were included if they were undertaken in children with relapsing SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents and outcome data at six months. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty trials involving 923 children were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13). Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the effect was not sustained when cyclosporin was ceased. During treatment, levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than steroids alone but the effect was not sustained. Mizoribine (one trial) and azathioprine (two trials) were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: Eight week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Clinically important differences in efficacy among these agents are possible and further comparative trials are still needed.
BACKGROUND: Eighty to ninety per cent of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in children who relapse frequently. However these non-corticosteroid agents also have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from proceedings and contact with known investigators. Search date: August 2004 SELECTION CRITERIA: RCTs or quasi-RCTs were included if they were undertaken in children with relapsing SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents and outcome data at six months. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty trials involving 923 children were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13). Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the effect was not sustained when cyclosporin was ceased. During treatment, levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than steroids alone but the effect was not sustained. Mizoribine (one trial) and azathioprine (two trials) were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: Eight week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Clinically important differences in efficacy among these agents are possible and further comparative trials are still needed.
Authors: Eiske M Dorresteijn; Joana E Kist-van Holthe; Elena N Levtchenko; Jeroen Nauta; Wim C J Hop; Albert J van der Heijden Journal: Pediatr Nephrol Date: 2008-07-12 Impact factor: 3.714
Authors: Marko Mrkobrada; Heather Thiessen-Philbrook; R Brian Haynes; Arthur V Iansavichus; Faisal Rehman; Amit X Garg Journal: Clin J Am Soc Nephrol Date: 2008-04-09 Impact factor: 8.237