Immunosuppressive treatment of children with relapsing nephrotic syndrome: a meta-analysis of randomised controlled trials

A Durkan, E Hodson, N Willis, J Craig

Centre for Kidney Research, Royal Alexandra Hospital for Children, P O Box 3515 Parramatta NSW 2124.

To evaluate the benefits and harms of non-steroid treatments used in children with steroid sensitive, relapsing nephrotic syndrome (NS), a meta-analysis of randomised controlled trials (RCTs) was performed by two independent reviewers. The Cochrane Controlled Trials Register, MEDLINE and EMBASE were searched, in addition to reference lists of text books, review articles, relevant trials and abstracts from nephrology meetings. Of 832 abstracts screened, 16 eligible trials were identified (total patient number n= 581). Overall study quality was poor. The three trials (n=106) comparing the use of cyclophosphamide (CPA) with steroid alone showed a reduction in relapse at 6-12 months, (summary relative risk, RR, of 0.44, 95% confidence interval, CI, 0.26-0.73). Chlorambucil (2 trials, n=41) also reduced the risk of relapse at 6-12 months, (RR 0.13,CI 0.03-0.57). Azathioprine (2 trials, n=60) and levamisole (3 trials,n=138) were not effective in reducing relapse rates (RR 0.90, CI 0.59-1.38 and RR 0.68,CI 0.38-1.24 respectively). Cyclosporin (CsA) was compared with chlorambucil in one trial which showed no significant difference between the 2 drugs at 6 months, (RR 0.80, CI 0.40-1.60) but there was a significant benefit of chlorambucil at 12 months (RR 0.50, CI 0.30-0.83). In this trial the CsA was only given for 24 weeks. When CsA was compared with CPA in a further trial, in which the CsA was given for 1 year, there was no significant difference in relapse rates at 12 months (RR 1.15,CI 0.47-2.86). The adverse effects were drug specific. Leucopaenia occurred with the alkylating agents. CPA was associated with hair loss (risk difference RD 0.52, CI 0.35-0.69). CsA was associated with hirsutism (RD 0.34, CI 0.21-0.46) and gum hyperplasia (RD 0.28, CI 0.16-0.41). There is evidence to support the use of alkylating agents as second line agents however no trial has directly compared CPA with chlorambucil. CsA has a role in the treatment of relapsing NS but its use is limited by the need to continue treatment for prolonged periods.

Presented at the Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology, Melbourne, March 2000

Correspondence
Elisabeth Hodson
ElisaH@chw.edu.au