Targeting CD20 for B-cell Depletion in Autoimmune Kidney Disease: Next Generation

Abstract

Anti-CD20 monoclonal antibodies are gaining clinical relevance in the nephrology community due to their demonstrated efficacy and favorable safety profiles across short-, medium-, and long-term use. Initially developed for hematologic malignancies and multiple sclerosis, B-cell depletion therapies are now being investigated across a broader spectrum of autoimmune diseases, including glomerulopathies, both with and without associated podocytopathy. Recent advances have led to the development of novel anti-CD20 agents that are being used not only as potential alternatives to corticosteroids but also as adjunctive therapies in complex clinical settings. However, their efficacy is not uniform across all conditions, whether used for induction therapy, relapse management, or as rescue treatment following first-line therapy failure. A thorough understanding of their mechanisms of action, along with the potential for resistance and therapeutic failure, is essential for advancing precision medicine in this field. This review provides a molecular and clinical overview, incorporating pharmacokinetic and pharmacodynamic insights into the most widely used and emerging anti-CD20 monoclonal antibodies in nephrology. It serves as a practical guide to understand how these agents’ function, why they may fail, and what alternative strategies should be considered in cases of adverse reactions or inadequate response. Finally, it highlights their evolving role in precision therapy, both as monotherapy in podocytopathies and as part of a multi-targeted treatment approach for glomerular diseases with systemic involvement.