B-cell depletion has spread across immune-mediated glomerular disease faster than the evidence distinguishing where it works. This KDIGO Controversies Conference, held in Panama City in June 2025 and reported in March, sorts it by disease — and the variation is the finding.
In membranous nephropathy, anti-CD20 antibodies are now first-line, with most patients achieving at least partial remission by 18 months. In ANCA-associated glomerulonephritis, rituximab is established for both induction and maintenance. In steroid-dependent nephrotic syndrome, rituximab prevents relapses, particularly in children, but the benefit is transient. In IgA nephropathy, rituximab has shown limited efficacy — while inhibitors of the B-cell survival factors BAFF and APRIL, and anti-CD38 antibodies, do reduce proteinuria and slow eGFR decline. In lupus nephritis, obinutuzumab and CAR T cells look promising, with CAR T raising the prospect of prolonged freedom from both disease activity and treatment.
Safety scales with intensity. Conventional anti-CD20 therapy has a favourable profile; CAR T cells demand careful patient selection because of cytokine release syndrome and other serious events. The conference names the gap that matters most: there are no validated biomarkers for deciding who should receive these therapies or for monitoring them, and optimal duration is unsettled in every indication.
- Do not generalise from membranous nephropathy to IgA nephropathy — rituximab is first-line in one and of limited use in the other.
- In IgA nephropathy, the B-cell agents worth watching are BAFF, APRIL and anti-CD38 inhibitors, not anti-CD20.
- Warn families in steroid-dependent nephrotic syndrome that rituximab delays relapse rather than ending it.
- Check immunoglobulin levels and vaccination status before any B-cell-depleting therapy, and revaccinate before rather than after.
- Treat CAR T in lupus nephritis as a specialist-centre option under trial conditions, not an available therapy.
Why it matters
"B-cell therapy works in glomerular disease" is a generalisation that fails in the commonest glomerulonephritis in the world.
Don't overread it
This is a conference consensus report identifying evidence and gaps, not a guideline with graded recommendations.
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