Authors of an exploratory study of 260 adults with biopsy-proven IgA nephropathy (IgAN) examined whether genetic variation in the complement system might influence disease susceptibility or kidney outcomes. In this French cohort, rare variants in six complement-related genes were more common among patients with IgAN than controls (16% vs 9%), driven largely by a higher prevalence of rare CFH variants. However, rare complement variants overall were not associated with kidney survival. Researchers also identified differences in CFH haplotypes that may be related to disease susceptibility, although these findings require confirmation.
The clearest prognostic signal involved the MCP/CD46 ggaac haplotype. Patients who were homozygous for this haplotype had a higher risk of progressing to end-stage kidney disease within 15 years, even after adjustment for factors including age, hypertension, eGFR, proteinuria, and biopsy findings (HR, 2.83). The findings support further investigation into whether inherited differences in complement regulation contribute to the variable course of IgAN. However, the authors emphasized that the study was exploratory, involved a relatively small cohort enriched for severe disease, and requires validation in larger, independent populations before complement genetics can inform clinical management.
Reference: Duval A, Maillard N, Morin M, et al. Association of Complement Genetics with Outcomes in IgA Nephropathy. Clin J Am Soc Nephrol. 2026 Jul 1;21(7):1207-1221. doi: 10.2215/CJN.0000001062.
