Single-dose versus multi-dose steroid therapy in pediatric nephrotic syndrome: a systematic review and meta-analysis

Corticosteroids remain the cornerstone of therapy for steroid-sensitive nephrotic syndrome (SSNS), yet the optimal dosing strategy, single daily versus divided doses, remains uncertain.

We conducted a systematic review of studies comparing once-daily and divided-dose prednisolone in children with SSNS. Three randomized controlled trials and one non-randomized study were included, enrolling a total of 288 patients. Primary outcomes were time to remission and relapse frequency; secondary outcomes included hypothalamic-pituitary-adrenal (HPA) axis suppression and adverse events.

Overall, remission rates were comparable between single and divided dosing. In relapse settings, one trial showed faster remission with split dosing (by 1-2 days), though without differences in relapse frequency or safety. In first-episode disease, single daily dosing was associated with less HPA axis suppression and a longer time to first relapse. Adverse event profiles were similar across regimens.

Single-dose and split-dose prednisolone regimens demonstrate comparable remission efficacy in children with SSNS. Divided dosing may shorten remission by 1-2 days during relapse episodes, but this small benefit must be weighed against the greater HPA-axis suppression observed with multi-dose schedules. Given the heterogeneity and small sample sizes of available trials, the current evidence remains insufficient to establish superiority. Larger multicenter RCTs with standardized protocols and longer follow-up are needed to provide more definitive guidance.