Single vs. Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children

Abstract

Background: Early morning single dose prednisolone has hypothetical advantage of less hypothalamic-pituitary-adrenal axis (HPA) suppression, but lack of robust evidence has resulted in variation in practice with divided dose prednisolone still commonly used. We conducted this open label randomized control trial to compare HPA axis suppression between single or divided dose prednisolone among children with first episode nephrotic syndrome. Methods: Sixty children with first episode nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided dose for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. Short Synacthen Test (SST) was conducted at 6 weeks with HPA suppression defined as post adrenocortopric hormone (ACTH) cortisol <18 µmg/dl. Results: Four children (single=1 and divided dose=3) did not attend SST and were hence excluded from analysis. Remission was induced in all and no relapse post remission was noted during the 6+6 weeks steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) vs single dose (83%) (p =0.02). Time to remission and final relapse rate were similar, but for those children who relapsed within 6 months of follow up period time to first relapse was shorter for divided dosing (median 28 vs 131 days) p=0.002. Conclusions: Among children with first episode nephrotic syndrome, single and or divided dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse.