Efficacy and safety of rituximab in adults with refractory nephrotic syndrome: a meta-analysis

Rituximab is effective in steroid‑dependent or frequently relapsing nephrotic syndrome, but its role across refractory disease—including steroid‑resistant patients and membranous nephropathy—and the determinants of response remain unclear. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library (January 2021 to August 2026) for studies of rituximab monotherapy in adults with refractory nephrotic syndrome. The primary outcome was complete remission at 12 months. Random‑effects meta‑analysis, subgroup analyses, and meta‑regression were performed; the certainty of evidence was assessed using GRADE. Twenty‑one studies (753 patients) were included. The complete remission rate was 88% ( I ²=0%) in steroid‑dependent or frequently relapsing patients, compared with 51% ( I ²=92.6%) in mixed or refractory patients ( p < 0.0001). A clear gradient emerged by pathology: minimal change disease 86% ( I ²=0%), focal segmental glomerulosclerosis 59% ( I ²=55.3%), and membranous nephropathy 38% ( I ²=95.8%) ( p = 0.0005). Within membranous nephropathy, prior calcineurin inhibitor response was a key determinant: CNI‑dependent patients achieved a complete remission rate of 84%, whereas CNI‑refractory patients achieved only 17% ( p = 0.0003), although these estimates were based on a limited number of studies. Meta‑regression demonstrated that each 10% increase in steroid‑resistant patients reduced the expected remission rate by 5.5% ( p < 0.001). Steroid withdrawal was achieved in approximately 80% of patients. Serious adverse events occurred in 2.3% (5/213) of patients among studies reporting this outcome, infusion reactions in 33.3% (16/48), and no treatment-related deaths were observed. Rituximab is highly effective in steroid‑dependent or frequently relapsing patients and in CNI‑dependent membranous nephropathy, with complete remission rates of approximately 85%. Efficacy was substantially lower in the CNI-refractory membranous nephropathy subgroup, with a complete remission rate of approximately 17%. Meta-regression showed that a higher proportion of steroid-resistant patients was associated with lower remission rates. Overall, these findings support a stratified, precision‑based approach to patient selection rather than empirical broad‑spectrum use.