Targeting B cells in immune-mediated kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.
A KDIGO Controversies Conference concluded that the effectiveness of B cell-targeted therapy varies substantially across immune-mediated kidney diseases — first-line in membranous nephropathy, of limited efficacy in IgA nephropathy, and promising but requiring careful patient selection for CAR T cells in lupus nephritis. Validating biomarkers for patient selection and monitoring was identified as a critical research need.
Background
Treatments that deplete or modulate B cells are already in use, or under investigation, for several immune-mediated glomerular diseases. KDIGO convened a Controversies Conference in Panama City, Panama, in June 2025 to review the current evidence and identify the key knowledge gaps and research needs for applying these therapies effectively.
Key findings
Availability, effectiveness and safety of B cell-targeted therapies vary substantially by disease. In IgA nephropathy, anti-CD20 therapy (rituximab) has shown limited efficacy, although inhibitors of the survival factors BAFF and APRIL and anti-CD38 antibodies can reduce proteinuria and slow the decline in estimated glomerular filtration rate. In membranous nephropathy, by contrast, anti-CD20 antibodies have become first-line therapy, achieving at least partial remission in most patients by 18 months. In steroid-dependent nephrotic syndrome, rituximab effectively prevents relapses, particularly in children, though the benefit is transient. For lupus nephritis, newer approaches including obinutuzumab and chimeric antigen receptor (CAR) T cell therapy have shown promising results, with CAR T cells raising the possibility of prolonged freedom from both disease activity and treatment. In ANCA-associated glomerulonephritis, rituximab is effective for both induction and maintenance, with trials of CAR T cell approaches ongoing.
Safety
Safety considerations vary with the intensity of therapy. Conventional anti-CD20 therapy shows a favourable safety profile, whereas CAR T cell therapy requires careful patient selection because of the potential for cytokine release syndrome and other serious adverse events.
Clinical implications
B cell-directed therapy cannot be applied uniformly across glomerular disease — the choice and intensity of agent should follow the disease-specific evidence. The conference identified validation of biomarkers for patient selection and monitoring as a critical research need, alongside optimising treatment protocols and determining the optimal duration of therapy.
Category
KDIGO
Source
Kidney Int
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