Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children, occurring in two of 100,000 children per year in Caucasians [
1]. Japanese children develop this disease at a three- to four-fold higher frequency than Caucasians [
2]. A total of 80–90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)] [
3]. Approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS), which is defined as at least four relapses per year or at least two relapses within 6 months of the initial presentation. A total of 50–60% of children with FRNS develop two consecutive relapses during tapering or within 14 days of stopping steroid therapy, which is referred to as steroid-dependent nephrotic syndrome (SDNS) [
4]. Standard treatments for FRNS or SDNS in children are immunosuppressive agents, including cyclophosphamide, chlorambucil, cyclosporine (CyA), tacrolimus and levamisole [
5]. The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerulonephritis recommends treatment with alkylating agents (such as cyclophosphamide or chlorambucil), levamisole, calcineurin inhibitors (including CyA or tacrolimus) and mycophenolate mofetil (MMF) as corticosteroid-sparing agents for children with FRNS or SDNS [
6]. The 2013 Clinical Practice Guidelines for Pediatric Nephrotic Syndrome of the Japanese Society for Pediatric Nephrology recommend CyA, cyclophosphamide or mizoribine as drug therapy for children with FRNS or SDNS [
7]. Although these treatments are generally successful in most patients, at least 10–20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment. Additionally, some patients with steroid-resistant nephrotic syndrome (SRNS) develop steroid-sensitive frequent relapses or steroid dependence after achieving complete remission by immunosuppressive therapies, including calcineurin inhibitors. A 5-year follow-up study of CyA treatment in children with SRNS showed that seven of 31 (23%) patients developed frequent relapses under immunosuppressive therapy after achieving complete remission [
8]. Therefore, these children require long-term steroid treatment, even though they experience serious side effects from the drug. We have defined these conditions as complicated FRNS or SDNS [
9‐
11]. In this review we also define FRNS or SDNS that has never been treated with immunosuppressive agents as uncomplicated FRNS or SDNS.
Rituximab is a chimeric anti-CD20 monoclonal antibody that inhibits CD20-mediated B-cell proliferation and differentiation. It was originally developed to treat patients with B-cell non-Hodgkin’s lymphoma. This monoclonal antibody is currently used for treating various autoimmune diseases, such as rheumatoid arthritis, Wegener’s granulomatosis and microscopic polyangiitis. In this review we highlight recent studies, mainly randomized, controlled trials (RCTs) of rituximab for SSNS, including complicated and uncomplicated forms of FRNS or SDNS, in children. We also discuss the effects of these studies on the management of patients suffering from these conditions.