Moreover, 80%C90% of children with SSNS experience relapses. however, a more targeted rituximab treatment did not significantly increase serum albumin levels and did not significantly reduce adverse events. Rituximab might be a promising treatment for childhood refractory nephrotic syndrome; however, the long-term effects and cost-effectiveness of rituximab treatment were not fully assessed, and there were limited studies that evaluated the clinical benefits of a concurrent infusion of rituximab plus a steroid compared with an infusion CHMFL-KIT-033 of rituximab only. Additional studies are required to address these issues. Nephrotic syndrome (NS) is a disorder characterized by large amounts of proteinuria, hypoalbuminemia, edema, and hyperlipidemia1. This disorder affects the kidneys by increasing the permeability of the glomerular basement membrane. NS occurs in 16 of every 100,000 children and is a major challenge in pediatric nephrology2. Moreover, NS CHMFL-KIT-033 places a large financial burden on the patient’s family. Although most affected children have steroid-sensitive nephrotic syndrome (SSNS), approximately 20% of children do not achieve complete remission and have steroid-resistant nephrotic syndrome (SRNS)3. Moreover, 80%C90% of children with SSNS experience relapses. Among these relapsing children, 50% relapse frequently and develop steroid-dependent nephrotic syndrome (SDNS)4,5,6. The long-term use of corticosteroids can adversely affect children’s growth and development7. The treatment of SRNS, SDNS, and SSNS remains challenging. Patients with SRNS who do not achieve remission will develop end-stage renal failure. The exact CHMFL-KIT-033 pathogeneses of SRNS, SDNS, and SSNS have not been fully elaborated, but immunological factors might play a vital role, and the use of immunosuppressants and immunological treatment interventions appear to have achieved promising results7. These immunosuppressants include cyclophosphamide8,9, chlorambucil10, cyclosporin11, levamisole12, and mycophenolate mofetil11. However, some of these immunosuppressants can have serious adverse effects such as nephrotoxicity, hyperglycemia, headaches and dyslipidemia13. Novel drugs are needed to address these problems. Rituximab is a monoclonal antibody that acts directly against CD20 expressed on B lymphocytes. It is widely used to treat lymphoma14 and rheumatoid arthritis15. Rituximab administration results in rapid and sustained B cell depletion. Several reports have proposed rituximab as a new treatment strategy for children with SDNS or SSNS13,16,17. However, the use of rituximab in the treatment of steroid- and calcineurin inhibitor-dependent SSNS requires further investigation. A single open-labeled, randomized controlled trial (RCT) that enrolled 54 children with SDNS who were dependent on prednisone and calcineurin inhibitors found that rituximab significantly reduced the relapse rate at 3 CHMFL-KIT-033 months (18.5% and 48.1% in the experimental and control arms, respectively), and it also increased the likelihood of NSHC a child not requiring prednisone or calcineurin inhibitor treatment18. Many studies have reported that rituximab treatment prolonged remission in patients with refractory NS19. The aim of this study was to combine the current evidence from all eligible comparative studies to systematically evaluate the use of rituximab versus current immunosuppressive agents in treating children with refractory NS. Methods Literature search This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement20. Our meta-analysis searches were conducted using the PubMed, Web of Science Knowledge and Cochrane Library databases from their inception dates to August 1, 2014. The search applied the following search terms: rituximab, CD20, and nephrotic syndrome. Study selection criteria and study types RCTs or comparative cohort studies that evaluated the efficacy and safety of rituximab in treating pediatric patients with refractory NS were included. Type of participants The patients were diagnosed with NS at 18 years of age and younger. Type of interventions Rituximab and current immunotherapy were compared. Different schedules and modalities of rituximab were included. Analyzed outcomes The primary outcome was relapse-free survival. The secondary outcomes were (1) complete remission events, (2) biological indicators, including CHMFL-KIT-033 proteinuria, serum albumin, serum cholesterol and serum creatinine, and (3) adverse events. Study selection and data extraction The references obtained from the electronic search were evaluated by two independent reviewers (Zhao Z and Liao G) using a study selection form. The initial assessment was based on screening the titles and abstracts; studies that did not meet the inclusion criteria were excluded. The studies that were not excluded after an initial evaluation were retrieved for full text screening and, according to the inclusion criteria, it was determined whether the study should be included in our analysis. In cases of disagreement, the final decision for inclusion was made by consensus among the authors. Review articles, case reports, comments, meeting abstracts and editorials were excluded. The data were extracted by two independent reviewers (Zhao Z and Liao G)..