DOI: 10.2215/cjn.0000000000000290 ISSN:

Mesangial C3 Deposition, Complement-Associated Variant, and Disease Progression in IgA Nephropathy

Yuqi Kang, Boyang Xu, Sufang Shi, Xujie Zhou, Pei Chen, Lijun Liu, Yebei Li, Yueqi Leng, Jicheng Lv, Li Zhu, Hong Zhang
  • Transplantation
  • Nephrology
  • Critical Care and Intensive Care Medicine
  • Epidemiology


IgA nephropathy is the most common primary glomerulonephritis worldwide, with dominant deposition of IgA and co-deposits of complement component 3 (C3). Phenotypes and progression of IgA nephropathy varies among different ethnic populations, while IgA nephropathy patients from Asian showed more severe clinical phenotypes, active kidney lesions, and rapid progression. Our previous genome-wide association study identified complement factor H variant rs6677604, tightly linked with the deletion of complement factor H-related protein 3 and complement factor H-related protein 1 genes (ΔCFHR3-1), as IgA nephropathy susceptible variant, and additionally revealed its effect on complement regulation in IgA nephropathy.


To further explore the effect of rs6677604 on IgA nephropathy progression, here we enrolled a Chinese IgA nephropathy cohort of 1781 patients with regular follow-up for analysis. The rs6677604 genotype was measured, and the genotype-phenotype correlation was analyzed using t-test, Chi-squared test, or nonparametric test, as well as the association between rs6677604 genotype or mesangial C3 deposition and IgA nephropathy prognosis was analyzed using Kaplan–Maier analysis and Cox regression.


We found that patients with rs6677604-GG genotype had a stronger intensity of mesangial C3 deposition than those with the rs6677604-AA/AG genotype. Patients with IgA nephropathy who had stronger intensity of C3 deposition manifested with more severe clinical and pathological manifestations, including lower eGFR and higher Oxford-M/S/T/C scores. In the survival analysis, stronger intensity of mesangial C3 deposition, but not rs6677604-GG genotypes, was associated with poor long-term kidney outcome in IgA nephropathy.


We found that in Chinese patients with IgA nephropathy, variant rs6677604 was associated with mesangial C3 deposition, and mesangial C3 deposition, but not rs6677604, was associated with IgA nephropathy severity and progression.

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