Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients

Abstract

Vascular endothelial growth factor (VEGF) was recently shown to predict survival in prevalent haemodialysis patients. Soluble VEGF receptors (sVEGFR)-1 and -2 are circulating endogenous modulators of VEGF activity. We thus studied the relationship between sVEGFR-1 and -2 and survival in a cohort of prevalent haemodialysis (HD) patients. Components of the VEGF system were measured (ELISAs) in 185 prevalent HD patients and levels related to clinical characteristics, biochemical markers and survival. The patients were followed up prospectively for a median 31 (20-37) months. While ischaemic heart disease was independently associated with a lower sVEGFR-2 (OR = 2.75, P = 0.02), sVEGFR-1 was positively associated with IL-6 (rho = 0.22, P = 0.003) and white blood cell count (rho = 0.22, P = 0.002). In survival analysis, the patients with a high sVEGFR-1 level had a higher all-cause mortality (Kaplan-Meier Chi-Square = 5.6, P = 0.02) and a higher adjusted mortality risk (Cox HR = 1.93, P = 0.009) than those with low levels. In the first clinical study of sVEGFR-1 and -2 in CKD, we found novel associations between the sVEGFRs and cardiac disease. This may be of clinical importance, as a high sVEGFR-1 was an independent risk factor for all-cause mortality.