Predictive prognostic value of glomerular C3 deposition in IgA nephropathy

Background IgAN is the most common primary glomerulonephritis worldwide. However, the pathogenesis of IgAN remains unknown. Currently, there is evidence that C3 deposition plays a role in disease development. This study aimed to investigate clinical, pathological features, and prognosis of adult IgAN patients with C3 deposition, as well as explore the role of complement activation in disease progression. Methods A total of 821 patients with biopsy-proven IgAN were included in this study. Patients were divided into three different groups according to their C3 deposition intensity. Clinical and pathological characteristics were compared between groups. Logistic analysis was used to estimate the relationship between C3 deposition and the Oxford scoring system. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of the presence of C3 deposits on the prognosis of patients with IgA nephropathy. Kaplan–Meier survival analysis was used to evaluate the cumulative incidence of renal progression between groups. Results Patients with C3 deposition exhibited more severe clinical and pathological features and had a higher score according to the Oxford scoring system. With the increasing intensity of C3 deposition, patients present more hematuria, crescents, heavier interstitial inflammatory cell infiltration and a higher score on segmental sclerosis lesions. Logistic regression identified a positive relationship between C3 deposition and histopathology. Univariate and multivariate Cox regression indicated that C3 deposition was an independent risk factor for IgAN severity. The Kaplan–Meier survival curves indicated that patients with positive C3 deposition had a worse prognosis compared to those without C3 deposition. Conclusions Patients with positive glomerular C3 deposition presented with more severe clinical and histopathological characteristics and a higher score on the Oxford scoring system. With the increasing intensity of C3 deposition, IgAN patients were more likely to present with high level of microscopic hematuria, fibrous crescents, interstitial inflammatory cell infiltration, and a higher score on segmental sclerosis lesions. C3 deposition at the time of renal biopsy is likely an independent risk factor for IgA nephropathy severity and progression. Graphical abstract