The 2025 International Society of Nephrology Forum on Complement Therapeutics brought a global panel together to answer a question the trials created rather than settled. Alternative pathway complement inhibitors have now succeeded in C3 glomerulopathy, primary immune-complex membranoproliferative glomerulonephritis and IgA nephropathy. How to use them outside a trial is unresolved.
The forum is clear about the biology, and the distinction matters for how confidently the drugs should be reached for. In C3G and IC-MPGN, complement overactivation is the primary driver - these are prototypical complement disorders. In IgA nephropathy it is not: complement appears to act as a secondary amplifier of damage in a disease with several other drivers. The same class of drug is therefore doing two different jobs.
The panel named four things that might select patients - complement biomarkers, complement autoantibodies, genetics, and the kidney biopsy - and concluded that none of them is established for that purpose. That is the honest state of the field, and it is worth saying to a patient who has read about these drugs. Until selection is solved, the reasonable position is that complement inhibition has a defined place in the complement-driven diseases and a less defined one in IgA nephropathy, where it sits alongside rather than instead of supportive therapy and the established agents.
- Separate the two indications in your own thinking: primary complement disease in C3G and IC-MPGN, secondary amplification in IgA nephropathy.
- Do not treat a complement biomarker or autoantibody result as a licence to start - the forum found none validated for selection.
- Keep the kidney biopsy in the pathway; its role in guiding complement therapy is unsettled, not dispensable.
- Maintain maximal supportive therapy in IgA nephropathy regardless of what else is added.
- Access is the practical barrier in most of the world - factor cost and availability into the conversation before raising the option.
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