RITUXIMAB IN MEMBRANOUS NEPHROPATHY: PATHOPHYSIOLOGY, CLINICAL EFFICACY AND EMERGING STRATEGIES FOR OPTIMIZED THERAPY

Spandana A.*, Amith M. N.

ABSTRACT

Membranous nephropathy (MN) stands as the principal cause of primary nephrotic syndrome in adults globally, characterized by autoimmune-mediated podocyte injury primarily driven by autoantibodies against the M-type phospholipase A2 receptor (PLA2R). The advent of rituximab, a chimeric anti-CD20 monoclonal antibody that depletes B cells, has revolutionized MN treatment paradigms by targeting the immunologic basis of disease. Multiple randomized controlled trials and meta-analyses have demonstrated rituximab’s efficacy in inducing durable remissions with a superior safety profile compared to traditional immunosuppressive regimens such as calcineurin inhibitors and alkylating agents. Despite the wide adoption of rituximab, optimal dosing strategies remain a subject of debate, with emerging data supporting individualized regimens guided by pharmacokinetics and immune-monitoring. This comprehensive review synthesizes current understanding of MN pathogenesis, the scientific rationale for B cell–targeted therapy, critical evaluation of clinical trial data on rituximab, dosing protocols, safety profiles, and future directions aimed at personalized medicine. The review underscores rituximab’s central role in MN management and highlights key challenges and opportunities for optimizing patient outcomes in this complex autoimmune glomerulopathy.

Keywords: Membranous nephropathy, rituximab, PLA2R, B cell depletion, immuno-monitoring, dosing optimization.