Treatment of Membranoproliferative Glomerulonephritis with C3 Glomerulopathy in Adults (18+)
Clinical Scenario
Adults ≥ 18 years
This protocol is for adults aged 18 years or older diagnosed with C3 glomerulopathy (C3G) — a specific pattern of membranoproliferative glomerulonephritis — affecting either a native or a post-transplant kidney.
Treatment Goals
The key targets are a substantial, sustained reduction in proteinuria (assessed at 26 weeks and again at 12 months), stabilisation of eGFR by 6 months, and reduction in glomerular C3 staining on kidney biopsy by week 26.
Treatment Approach
Current evidence supports adding a proximal complement inhibitor on top of continued supportive care in adults with significant proteinuria at baseline. The full protocol specifies the eligible agents, their routes of administration, and all relevant criteria.
References
DOI: 10.1016/j.ekir.2025.10.020
In 2025, iptacopan was also approved by the US Food and Drug Administration for the treatment of adults with C3G to reduce proteinuria, and by the European Medicines Agency for the treatment of adults with C3G in combination with a renin-angiotensin-aldosterone system inhibitor or as monotherapy in patients who are renin-angiotensin-aldosterone system inhibitor-intolerant.
The phase 3 trial data suggest that we should be using these agents in patients with significant proteinuria at the outset.
Patients who achieve a UPCR < 0.88 g/g (< 100 mg/mmol) at 12 months after diagnosis benefit from a 90% lower risk of kidney failure than those who did not achieve this threshold.
For both C3G and primary IC-MPGN, a ≥ 50% proteinuria reduction after 12 months has consistently been associated with significantly lower risk of kidney failure, as demonstrated by both the UK RaDaR and Spanish GLOSEN registries.
In this context, even stabilization of eGFR may be considered a success after 6 months of complement inhibitor therapy, although it must be acknowledged that changes in eGFR are dependent on factors such as disease chronicity.
Pegcetacoplan treatment resulted in 74.3% (26/35) of patients achieving a meaningful reduction in staining (≥ 2 point improvement on the 0–3 scale) by week 26 and 71.4% (25/35) had zero C3 staining in the biopsy after treatment.
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