Serum C3/C4 ratio is a novel predictor of renal prognosis in patients with IgA nephropathy: a retrospective study

IgA nephropathy (IgAN) is an autoimmune disease associated with complement activation. It is unclear whether the ratio of serum C3 and C4 concentrations (C3/C4 ratio) can predict renal outcomes in IgAN patients. A total of 1503 patients diagnosed with IgAN via renal biopsy were recorded in this study. Poor renal outcomes were defined as > 50% decrease in the baseline estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD) during follow-up. In total, 712 patients meeting the exclusion/inclusion criteria were selected, and the mean follow-up period was 40.6 (12.34) months. Patients with decreased C3/C4 ratios displayed significantly more severe clinical characteristics and renal pathological features and a higher proportion of poor renal outcomes and ESRD. The optimal multivariate Cox regression models identified the C3/C4 ratio (hazard ratio (HR) 0.63, 95% CI 0.5–0.9), serum uric acid (HR 1.58, 95% CI 1.2–2.2), serum creatinine (HR 1.3, 95% CI 1.1–1.6), systolic blood pressure (HR 1.57, 95% CI 1.2–2.0) and T score (relative to T0, T1: HR 1.96, 95% CI 1.1–3.7, T2: HR 3.03, 95% CI 1.6–5.9) as strong predictors of poor renal outcomes. Subgroup analysis showed that patients with low C3/C4 ratios benefited from glucocorticoids or other immunosuppressive agents (hazard ratio 0.30 and 0.18, 95% CI 0.13–0.72 and 0.07–0.46, respectively). Serum C3/C4 ratios may be an independent novel predictor of renal outcomes in IgAN patients. Decreased C3/C4 ratios suggest poor renal outcomes and the potential to benefit from aggressive immunosuppressive therapies.