MONOCLONAL ANTIBODIES IN NEPHROLOGY

Abstract Monoclonal antibodies have revolutionized renal medicine by enabling targeted modulation of immune pathways involved in glomerular, vascular, and transplant-related kidney diseases. Unlike conventional immunosuppressants, monoclonal antibodies bind specific antigens with high affinity, improving efficacy while reducing off-target toxicity. Their impact has been particularly significant in autoimmune glomerulopathies, complement-mediated disorders, and antibody-mediated transplant rejection. Many renal diseases are immune-mediated, involving B-cell dysregulation, autoantibody production, immune complex deposition, complement activation, and inflammatory cytokines. Rituximab, an anti-CD20 monoclonal antibody, depletes B cells through complement-dependent and antibody-dependent cytotoxicity. It has shown strong efficacy in membranous nephropathy and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, and although early trials in lupus nephritis were inconclusive, it remains useful in selected or refractory cases. Second-generation anti-CD20 agents, such as obinutuzumab, demonstrate enhanced cytotoxicity and promising results in lupus nephritis. Complement inhibition represents another major advance. Eculizumab, a C5 inhibitor, has dramatically improved outcomes in atypical hemolytic uremic syndrome, while ravulizumab offers extended dosing with similar efficacy. Complement blockade is also being explored in C3 glomerulopathy and transplant rejection. Emerging therapies include iptacopan, targeting factor B of the alternative pathway, and sutimlimab, inhibiting C1s in the classical pathway. Other strategies include interleukin-6 receptor blockade with tocilizumab and B-cell activating factor (BAFF) inhibition with belimumab in lupus nephritis. Despite clear benefits, monoclonal antibodies carry infection risks, infusion reactions, and high costs. Overall, they represent a cornerstone of precision-based nephrology, with ongoing research refining patient selection and long-term outcomes.