Research Advances in Rituximab-Resistant Membranous Nephropathy

Membranous nephropathy is an autoimmune disease associated with antibodies against podocyte proteins, and it is the main cause of nephrotic syndrome in adults. Rituximab has now become the first-line treatment for membranous nephropathy, with 80% of patients achieving remission. However, some patients develop drug resistance or experience relapse to rituximab. Potential resistance mechanisms include changes in bioavailability and pharmacokinetics, rituximab internalization by B cells, memory B cells escape from rituximab, generation of anti-rituximab antibodies, impact of phospholipase A₂ receptor antibodies and epitope spreading, and chronic and irreversible kidney injury. Understanding these specific resistant mechanisms has driven the development of multiple therapies. Emerging treatments, including next-generation anti-CD20 monoclonal antibodies, B lymphocyte stimulator inhibitors, proteasome inhibitors, complement inhibitors, and plasma cell-targeted drugs, offer new hope for these patients. This review summarizes the potential mechanisms of rituximab resistance in membranous nephropathy and recent therapeutic advances, aiming to provide guidance for clinical management of membranous nephropathy.