Practice variation in the use of steroid-sparing therapies in childhood steroid-sensitive nephrotic syndrome: results from a prospective cohort study

Pediatr Nephrol. 2025 Jul 1. doi: 10.1007/s00467-025-06853-8. Online ahead of print.

Abstract

Background: Steroid-sparing therapies are often used to prolong disease remission while minimizing steroid toxicity in childhood steroid-sensitive nephrotic syndrome (SSNS). This study aims to describe practice variation in the use of steroid-sparing medications for childhood SSNS in Canada.

Methods: Children (1-18 years) with nephrotic syndrome (NS) from eleven pediatric nephrology centers in Canada were enrolled in the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) prospective cohort from 2013-2019. Data, including time to first relapse for children treated with cyclophosphamide, tacrolimus, mycophenolate mofetil, cyclosporine and rituximab were analyzed using summary statistics. Participants who received steroid-sparing therapies prior to enrolment were excluded.

Results: Of the 371 children enrolled, 321 (86.5%) had SSNS and 133 met the study criteria. Median age at enrollment was 3.0 years (IQR: 2.0-6.3). Median follow-up period was 3.0 years (IQR 1.0-4.0). Timing of initiation and choice of steroid-sparing therapy varied across centers. The majority (72.2%) initiated therapies after a median of 3 relapses (IQR: 2-4). Cyclophosphamide and tacrolimus were the most frequently used initial therapies at 39.1% and 23.3%, respectively. Thirty (22.6%) patients switched to a second medication after a median time of 4 months (IQR 0.25-11); of which, 40% switched from either cyclophosphamide or mycophenolate mofetil to tacrolimus. There were no statistically significant differences in time to first relapse with initial therapies (log rank P-value 0.36).

Conclusions: Significant variation in the use of steroid-sparing therapies exists in the treatment of SSNS. A clinical trial is needed to examine the efficacy of these medications to optimize treatment and decrease practice variation.

Keywords: Children; Practice variation; Prospective cohort; Steroid-sensitive nephrotic syndrome; Steroid-sparing medications.