CYCLOSPORINE VERSUS CYCLOPHOSPHAMIDE FOR PATIENTS WITH STEROID-DEPENDENT AND FREQUENTLY RELAPSING IDIOPATHIC NEPHROTIC SYNDROME - A MULTICENTER RANDOMIZED CONTROLLED TRIAL

Objective. To compare the efficacy (maintenance of remission), safety and tolerability of cyclosporin (CsA) with those of cyclophosphamide i n patients with steroid-dependent or frequently relapsing nephrotic sy ndrome (NS). Design. Open, prospective, randomized, multicentre, contr olled study for parallel groups, stratified for adults and children. T he setting was in nephrological departments in Italy. Subjects and int erventions. Seventy-three patients with steroid-sensitive idiopathic N S admitted to the study were randomly assigned to cyclophosphamide (2. 5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6 mg/kg/day in children) for 9 months, tapered off by 25% every month until complete discontinuation at month 12. Seven patients lost to follow up were no t considered in the analysis. The remaining 66 patients were followed up for 3-24 months after randomization. Main outcome measures. Relapse -free survival; number of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory investigations (kidney and liver fun ctions, haematological parameters); incidence of adverse events.Result s. At month 9, 26 of 35 CsA-treated patients were still in complete re mission and a further five patients were in partial remission; 18 of 2 8 cyclophosphamide-treated patients were in complete remission, and on e in partial remission (P=NS). No difference between adults and childr en was seen with either treatment. The risk of relapse was similar bet ween frequent relapsers (19 of 22) and steroid-dependent patients(8 of 14) given CsA, and those given cyclophosphamide (5 of 15 and 6 of 15) . The mean number of relapses per year and the mean dose of prednisone per year were significantly less (P<0.001) in both groups for the exp erimental year than for the year before randomization. At 2 years, 25% of the patients given CsA (50% adults and 20% children) and 63% of th ose given cyclophosphamide (40% adults and 68% children) had not had a ny relapse of NS. Tolerance to the two drugs was generally good. The C sA-related side-effects were mild and disappeared after drug discontin uation. Conclusions. This study shows that both treatments are effecti ve and well tolerated; more patients given cyclophosphamide had stable remissions.