Single- versus Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children: An Open-Label RCT.

BACKGROUND

Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis 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-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome.

METHODS

Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl.

RESULTS

Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002.

CONCLUSIONS

Among children with first episode of nephrotic syndrome, single-dose 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.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CTRI/2021/11/037940.

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