IgA nephropathy has gone from a disease with almost nothing to offer to the most active area in glomerular disease within a few years, and the guideline process has struggled to keep up. KDIGO updated its glomerular disease guideline in 2021 after more than a decade, then updated the IgA nephropathy section again in 2025 — and three further treatments received accelerated FDA approval after that revision went to press.
Rather than reopen the whole guideline, the IgA nephropathy Work Group has issued a commentary. The reason given is specific: two of the three newly approved therapies work through mechanisms different from the drugs already approved, so it is not obvious from the existing guideline where they belong in a treatment sequence. The commentary sets out provisional positioning, explicitly pending further evidence for these and other agents.
The framing is the useful part. Accelerated approval means a drug reached the market on a surrogate endpoint — in this disease, almost always proteinuria reduction — with confirmatory outcome data still to come. So the question a nephrologist faces is not whether these drugs lower proteinuria, which is established, but where they sit relative to supportive care, RAS blockade, SGLT2 inhibition and the agents already in the guideline. That is a sequencing question the trials were not designed to answer, and a work group commentary is the appropriate instrument for it.
For Indian practice the relevance is mostly about the next few years rather than this week. IgA nephropathy is common here and presents with more advanced disease than in Western cohorts, and none of these agents is affordable at scale. But the sequencing logic matters regardless of which drugs are available: optimise supportive therapy and RAS blockade fully, add an SGLT2 inhibitor, reassess proteinuria, and only then consider a targeted agent. That order is what stops an expensive drug being used to compensate for incomplete basic treatment.
- KDIGO has issued a commentary, not a full guideline update, on three newly approved IgA nephropathy therapies.
- Two of the three act through mechanisms different from previously approved drugs, hence the sequencing question.
- Accelerated approvals rest on proteinuria reduction; confirmatory outcome data are still pending.
- Optimise supportive care, RAS blockade and SGLT2 inhibition before considering a targeted agent.
- Reassess proteinuria after full supportive therapy — that measurement drives the next decision.
The statistics, in plain English
Accelerated approval is a regulatory pathway, not a level of evidence. It allows a drug to market on a surrogate endpoint reasonably likely to predict benefit, with confirmatory trials required afterwards — and those confirmatory trials sometimes fail. In IgA nephropathy the surrogate is proteinuria, which correlates well with kidney survival across populations but does not guarantee that lowering it in an individual on a given drug prevents kidney failure. A KDIGO commentary rather than a guideline update signals exactly this: the work group considers the evidence insufficient to make graded recommendations yet.
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