Preserved Linear Growth in Children with Difficult-to-Treat Nephrotic Syndrome: A 25-Year Longitudinal Cohort Study.

Abstract

Objective: Difficult-to-treat nephrotic syndrome (NS), including frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS) forms, often requires prolonged corticosteroid therapy and may adversely affect linear growth. Although steroid-sparing agents are increasingly used, longterm growth outcomes in this population remain insufficiently defined. This study aimed to evaluate long-term growth patterns and the impact of cumulative steroid exposure and steroid-sparing therapies in children with difficult-to-treat NS.

Methods: This single-center retrospective cohort study included 57 children with difficult-to-treat NS (38 SDNS/FRNS, 19 SRNS) followed between 2000 and 2025. Height standard deviation scores (SDS) at baseline, last follow-up, and estimated target height were assessed, and a decline of >1 SDS was evaluated as a clinically relevant outcome. Cumulative steroid dose, time-weighted steroid exposure using area under the curve (AUC), average daily steroid exposure, and the use of steroid-sparing therapies were recorded.

Results: The median follow-up duration was 7.5 years, and median age at last visit was 15 years. Median cumulative steroid exposure was 431 mg/kg, with a steroid AUC of 511 mg/kg*year and an average daily steroid exposure of 0.18 mg/kg/day. Short stature was observed in one patient (2%). Height SDS at the final evaluation did not differ from baseline or target height, and similar findings were observed in SDNS/FRNS and SRNS subgroups. Overall, 46 patients (81%) had stable or improved height SDS, while 11 patients (19%) showed a decline of >1 SDS. No clinical, histopathological, or treatment-related factors were associated with height SDS decline.

Conclusions: Long-term linear growth was largely preserved in children with difficult-to-treat NS, and short stature was uncommon. Favorable growth outcomes appear achievable with contemporary management strategies incorporating effective disease control and steroid-sparing therapy.