Extending Prednisolone Treatment Does Not Reduce Relapses in Childhood Nephrotic Syndrome

Abstract

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m 2 ). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration.

Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children

“…Prednisone is the cornerstone of therapy for idiopathic nephrotic syndrome, inducing remission within 4-6 weeks in approximately 90% of cases (7). However, the risk of relapse can be as high as 85% at 5 years, requiring reiteration of prednisone courses, often with the additional use of calcineurin inhibitors.…”

Corticosteroids for the initial episode of steroid-sensitive nephrotic syndrome

“…Only three studies showed adequate allocation concealment [12][13][14], and no studies were blinded. In contrast, three [5][6][7] of the four studies added to the 2015 update demonstrated adequate allocation concealment, and two studies were blinded [5,7].…”

“…Three large well-designed RCTs were published in 2013-2015 [5][6][7] which evaluated different durations of prednisolone therapy in children with their first episode of SSNS. In their RCT, Teeninga and co-workers [5] randomized 150 children to 3 months of prednisolone therapy and 3 months of placebo, or to 6 months of prednisolone therapy, with both groups receiving approximately the same total dose of prednisolone.…”

“…In their RCT, Teeninga and co-workers [5] randomized 150 children to 3 months of prednisolone therapy and 3 months of placebo, or to 6 months of prednisolone therapy, with both groups receiving approximately the same total dose of prednisolone. The cumulative incidences of children with FRNS did not differ between treatment groups for up to 5 years, suggesting that the apparent benefit of prolonged treatment of SSNS resulted from the increased total dose of prednisolone-and not the duration of the therapy.…”

The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence

“…3 However, frequent relapses and steroid dependence are disease outcomes in about 20%-60% of affected children. 4 Conversely, FSGS is characterized by steroid resistance in a majority of patients, steroid sensitivity in only about 20% of cases, as well as a high risk of developing end-stage renal disease. 5 Various hypotheses regarding the pathogenesis of the syndrome have evolved over time, with the current paradigm revolving around a podocytopathy.…”