Rituximab for nephrotic syndrome in children

Kazumoto Iijima,Mayumi Sako,Kandai Nozu

doi:10.1007/s10157-016-1313-5

Abstract

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

Highlights

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children, occurring in two of 100,000 children per year in Western countries [1] and in five of100,000 children per year in Japan
1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS
This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated frequently relapsing nephrotic syndrome (FRNS)/steroid-dependent nephrotic syndrome (SDNS)

Summary

Introduction

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children, occurring in two of 100,000 children per year in Western countries [1] and in five of. An open-label, randomized, controlled trial showed that rituximab plus lower doses of prednisone and calcineurin inhibitors were noninferior to standard doses of these agents in maintaining short-term remission in children with steroid- and calcineurin inhibitor-dependent nephrotic syndrome (i.e., complicated FRNS/SDNS) [36]. These two studies were investigator-initiated clinical trials to gain approval from the Ministry of Health, Labour and Welfare of Japan for rituximab treatment of patients with childhood-onset complicated FRNS/SDNS In these studies, patients who had a relapse of nephrotic syndrome were treated with protocol-defined prednisolone therapy and underwent screening examinations. In patients with calcineurin inhibitor-dependent, steroid-resistant nephrotic syndrome, the mean relapse rate during 6 months after rituximab treatment was significantly lower than that before treatment (2.0 vs 0.2). The relapse rate was significantly lower in the rituximab than in the placebo group [1.542 (29/18.81) vs

B Treatment failure-free survival probability

Conclusions and future perspectives

Findings

Compliance with ethical standards