Short Versus Long Steroid Therapy in Nephrotic Syndrome

Abstract

Source: Pasini A, Bertulli C, Casadio L, et al. Childhood idiopathic nephrotic syndrome: does the initial steroid treatment modify the outcome? A multicentre, prospective cohort study. Front. Pediatr. 2021;9:627636; doi.10.3389/fped.2021.627636Investigators from multiple institutions in Italy conducted a prospective study comparing relapses in children with idiopathic nephrotic syndrome (INS) treated with different steroid regimens, with treatment based on time to remission (TTR). Study patients were children >6 months to <18 years old with a first episode of INS, defined as proteinuria >40 mg/m2/hr or urine protein/creatinine ration (uPr/UCr) >2 mg/mg, and serum albumin <2.5 g/dL who were treated at 49 different pediatric units in Italy between 2011 and 2016. Children with congenital or secondary nephrotic syndrome were excluded. TTR was defined as first day of negative/trace protein on daily dipstick assessment after initiation of treatment. Study patients with a TTR of ≤10 days received prednisone, 60 mg/m2/day for 4 weeks, while those with a TTR >10 days were treated with the same prednisone dose for 6 weeks. Both groups had the same steroid-tapering dose regimen. Study patients who did not achieve remission within 8 weeks were classified as steroid-resistant and excluded.Study participants were followed for 24 months, with relapses defined as 3 days of ≥2+ protein on urine dipstick confirmed by a uPr/UCr >2 mg/mg. Primary outcomes included any relapse, time to first relapse and number of relapses. These outcomes were compared between those with a TTR ≤10 days (group A) and those with a TTR >10 days (group B) using chi-square or non-parametric (Wilcoxon, Krukal-Wallis) tests. A Kaplan Meier analysis was used to compare relapse-free survival in patients in groups A and B.A total of 184 children were enrolled in the study, but 21 steroid-resistant and 20 non-compliant patients were excluded from the analyses. Among the remaining 143 participants, 100 (70%) had a TTR ≤10 days (group A) and 43 had a longer TTR (group B). Children in group A were significantly older (mean ages 4.73 and 4.14 years, respectively; P = 0.01) and had a lower mean uPr/UCr than those in group B. A relapse occurred in 118 (78%) participants, including 77% of those in group A and 79% of group B patients (P = 0.91). There was also no difference in number of relapses between participants in group A and B (mean number 1.8 and 2, respectively; P = 0.43). Mean time to first relapse was longer for children in group A than group B (206 vs 167 days; P = 0.05), but relapse-free survival was not significantly different between groups.The authors conclude that in children with INS, different steroid regimens, based on TTR, were not associated with risk of relapse.Dr Sanchez-Kazi has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Nephrotic syndrome is one of the most common glomerular disorders in children.1 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend treatment of the initial episode with 60 mg/m2 or 2 mg/kg daily for 4–6 weeks (maximum 60 mg) followed by alternate day prednisone at 40 mg/m2 or 1.5 mg/kg x 2–5 months with tapering of the dose.2 The current investigators assessed whether induction therapy of 4 weeks vs 6 weeks with the same duration of weaning will alter the frequency of relapses and development of frequently relapsing INS.There may be an inherent fault in the trial since the investigators used TTR as the randomization criterion. The results of previous studies demonstrated that TTR is not a significant factor in the prediction of the number of relapses in steroid sensitive INS.1 It would have been better if the randomization was done based on age. As reported in the current study, the younger age group had a higher number of relapses despite longer induction. Similar findings were reported in a meta-analysis of European children less than 4 years of age.1,3 Multiple randomized controlled studies in different countries also have shown that the standard therapy and further extension of the standard therapy did not alter the risk of frequent relapses in steroid sensitive INS (See AAP Grand Rounds. 2020;43:32.)4-7Shorter steroid therapy was not only cost-effective but associated with fewer adverse effects on growth and behavior due to lower cumulative dose.5–6 In the future, biomarkers may be useful in risk stratification of patients with steroid-sensitive INS and modifying the frequency of relapses.Duration and dose of steroid induction therapy do not modify the number of relapses in steroid-sensitive INS in children.