Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome.

Background: It has been demonstrated that alkylating agents such as cyclophosphamide (CYP) are effective in reducing the risk of relapse in frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS). Little is known about prognostic factors in SDNS and FRNS treated by CYP. The objectives of this study are to determine long-term outcomes and factors associated with sustained remission in these patients.

Methods: We retrospectively studied the data from 143 children (104 boys) with SDNS and FRNS treated with CYP in six centres over 15 years. Relapse-free survival was estimated by Kaplan-Meier method. The determinants of long-term remission were assessed by univariate and multivariate analyses using Cox proportional hazard models.

Results: Median age at diagnosis was 3.7 years (interquartile range: IQR 2.3-5.9), and median follow-up was 7.8 years (IQR 4.0-11.8). CYP treatment was introduced after a median time of 1.7 years (IQR 0.7-5.9) after diagnosis. Patients received a median cumulative dose of 168 mg/kg (IQR 157-197) body weight. Relapse-free survival was 65%, 44%, 27% and 13% after 6 months, 1 year, 2 years and 5 years, respectively. In multivariate analysis, sustained remission >2 years was associated with age at treatment >5 years (P = 0.02) and cumulative dose of CYP >170 mg/kg (P = 0.02). Frequently relapsing versus steroid-dependent status and female gender were predictors of borderline significance. Height and body mass index standard deviation score were significantly influenced by CYP treatment.

Conclusions: In our study, long-term efficacy of cyclophosphamide in steroid-responsive nephrotic syndrome is disappointing. Further well-designed trials are required to evaluate the efficacy of other steroid-sparing agents.