Prolonged remission after cyclophosphamide or tacrolimus treatment in childhood nephrotic syndrome: a cohort study.

Background: Steroid-sparing immunosuppression is used in 50% of children with nephrotic syndrome, to prevent relapses and steroid-related toxicity. However, rates and predictors of prolonged remission after cyclophosphamide and tacrolimus are uncertain.

Methods: Retrospective analysis of children (1-18 years) enrolled in a longitudinal cohort. We included children diagnosed with steroid-sensitive nephrotic syndrome between 1996-2019 from Toronto, Canada. The exposure was cyclophosphamide or tacrolimus initiation. The primary outcome was prolonged remission (no further relapse or steroid-sparing immunosuppression). We evaluated predictors of prolonged remission and calcineurin inhibitor nephrotoxicity by logistic regression.

Results: Of 578 children with steroid-sensitive nephrotic syndrome, 252 received cyclophosphamide and 120 received tacrolimus. Over median 5.4-year (IQR 2.4-9.1) follow-up, prolonged remission occurred in 72 (28.6%) after cyclophosphamide and 17 (14.2%) after tacrolimus. Relapse frequency decreased after initiation of either medication. Lower prior relapse rate, more recent treatment era, and female sex were predictive of prolonged remission after cyclophosphamide treatment. Use of tacrolimus as the first steroid-sparing medication was the only factor predictive of calcineurin inhibitor nephrotoxicity.

Conclusions: Less than one-third of children achieve prolonged remission after initiating cyclophosphamide or tacrolimus, although both reduce short-term relapse rates. Few factors predict prolonged remission after cyclophosphamide or tacrolimus use, or calcineurin inhibitor nephrotoxicity.