Targeting B cells in immune-mediated kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Abstract

Treatments that deplete or modulate B cells are in use or being investigated for several immune-mediated glomerular diseases. Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference in Panama City, Panama, in June 2025 to review current evidence and identify key gaps in knowledge and research needs to effectively apply such therapies. Availability, effectiveness, and safety of B cell-targeted therapies vary substantially across glomerular diseases. In IgA nephropathy, anti-CD20 therapy (rituximab) has shown limited efficacy, although inhibitors of survival factors B cell-activating factor and A proliferation-inducing ligand and anti-CD38 antibodies can lead to reduction in proteinuria and reduction in decline in estimated glomerular filtration rate. In contrast, for membranous nephropathy, anti-CD20 antibodies have become first-line therapy, achieving at least partial remission in most patients by 18 months. In podocytopathies, rituximab effectively prevents relapses in steroid-dependent nephrotic syndrome, particularly in children, though benefits are transient. For lupus nephritis, newer approaches including obinutuzumab and chimeric antigen receptor T-cell therapy have shown promising results, with chimeric antigen receptor T cells introducing the possibility of being free of disease activity and treatment for a prolonged time. In antineutrophil cytoplasmic antibody-associated glomerulonephritis, rituximab has proven effective for both induction and maintenance therapy, with ongoing trials investigating chimeric antigen receptor T-cell approaches. Safety considerations of B cell-targeting therapies vary by intensity of therapy, with conventional anti-CD20 therapy showing favorable safety profiles and chimeric antigen receptor T-cell therapy requiring careful patient selection because of the potential for cytokine release syndrome and other serious adverse events. Validating biomarkers for patient selection and monitoring is a critical research need, along with optimizing treatment protocols and determining optimal therapy duration.