Interventions for idiopathic steroid-resistant nephrotic syndrome in children

• Published in: Cochrane database of systematic reviews 2010-11 (11), p.CD003594-CD003594
• Main Authors: Hodson, Elisabeth M, Willis, Narelle S, Craig, Jonathan C
• Format: Article
• Language: English
• Subjects: Adolescent; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Azathioprine - therapeutic use; Child; Child, Preschool; Cyclophosphamide - therapeutic use; Cyclosporine - therapeutic use; Dexamethasone - therapeutic use; Drug Resistance; Humans; Immunosuppressive Agents - therapeutic use; Infant; Nephrotic Syndrome - drug therapy; Prednisone - therapeutic use; Proteinuria - prevention & control; Randomized Controlled Trials as Topic; Remission Induction
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD003594.pub4

The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. To evaluate the benefits and harms of interventions used to treat idiopathic steroid-resistant nephrotic syndrome (SRNS) in children. Randomised controlled trials (RCTs) were identified from the Cochrane Renal Group's specialised register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS. Two authors independently searched the literature, determined study eligibility, assessed quality and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. Fourteen RCTs (449 children) were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission (three studies, 49 children: RR 7.66, 95% CI 1.06 to 55.34). Cyclosporin significantly increased the number with complete or partial remission compared with IV cyclophosphamide (one study, 32 children: RR 3.40, 95% CI 1.12 to 10.28). There was no significant difference in the number who achieved complete remission between oral cyclophosphamide with prednisone versus prednisone alone (two studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (one study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide with IV dexamethasone (one study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), tacrolimus versus cyclosporin (one study, 41 children: RR 0.86, 95% CI 0.44 to 1.66) and azathioprine with prednisone versus prednisone alone (one study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). ACEi significantly reduced proteinuria (two studies, 70 children). No studies were identified comparing high dose steroids and cyclosporin with single agents,