Plasma C4 level was associated with mortality, cardiovascular and cerebrovascular complications in hemodialysis patients

Background Patients on maintenance hemodialysis (HD) exhibit a high risk of death, cardiovascular and cerebrovascular diseases (CCDs). Previous studies indicated complement activation associated with the increased risk of cardiovascular diseases in HD patients. This study aimed to explore whether the critical complement factors were associated with the adverse outcomes in HD patients. Methods A total of 108 HD patients were included and followed up for 52 months. The baseline clinical characteristics and plasma C3c, C1q, CFH, CFB, C4, MAC, C5a, C3a and MBL were measured. The three endpoints were death, cardiovascular and cerebrovascular events (CCEs) and the composition of them. Univariate and multivariate Cox regression identified factors associated with the three endpoints respectively. X-tile analyses determined the optimal cut-off values for high risks. Restricted cubic spline plots illustrated the dose-response relationships. Correlations between the complement factors and risk factors for CCDs were analyzed. Results Baseline plasma C4 was finally selected by univariate and multivariate Cox regression analyses for three endpoints, including all-cause mortality, CCEs and the composition of them. When baseline plasma C4 exceeded 0.47 (P = 0.001) or 0.44 (P = 0.018) g/L respectively, the risks for death or achieving the composite endpoint enhanced significantly. The relationships of C4 and HR for the three endpoints showed a positive linear trend. Plasma C4 had prominent correlations with blood TG (r = 0.62, P < 0.001) and HDL (r = -0.38, P < 0.001). Conclusions A higher baseline plasma C4 level was significantly associated with the future incidence of decease, CCEs and either of them. Plasma C4 level correlated with blood TG and HDL.