Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome

Children with steroid-sensitive nephrotic syndrome (SSNS) frequently experience relapses triggered by intercurrent infections, particularly upper respiratory tract infections (URTIs). Previous, smaller studies suggested that administering a short course of daily low-dose prednisolone at the start of a URTI could prevent these relapses. This study, the PREDNOS 2 trial, aimed to rigorously test this strategy in a large, multicenter, double-blind, placebo-controlled setting to determine its efficacy across a broader, more representative population of children.

Researchers recruited 365 children (aged 1-18) with relapsing SSNS from 122 pediatric departments across the UK. Participants were randomized to receive either a 6-day course of daily low-dose prednisolone (15 mg/m2) or a matching placebo at the onset of a URTI. The trial included children with various background immunosuppressive regimens or no background treatment. The primary outcome was the incidence of the first URTI-related relapse, with secondary outcomes covering overall relapse rates, cumulative steroid exposure, adverse events, and quality of life.

In the modified intention-to-treat analysis of 271 children, there was no statistically significant difference in the incidence of URTI-related relapses between the prednisolone arm (42.7%) and the placebo arm (44.3%). Furthermore, no significant differences were observed in secondary outcomes, including overall relapse rates, the need for escalation of background immunosuppressive therapy, or corticosteroid-related adverse effects. A post hoc subgroup analysis hinted at potential differences in treatment response based on ethnicity, but these results were not statistically significant and require further investigation.

These findings challenge the previous consensus derived from smaller, less robust studies that supported the use of prophylactic prednisolone during infections. By demonstrating that this intervention provides no clinical benefit in a large, diverse cohort, the PREDNOS 2 trial provides high-quality evidence that should inform clinical practice and likely shift the conclusions of future meta-analyses regarding the management of childhood nephrotic syndrome.