Resistin and all-cause and cardiovascular mortality: effect modification by adiponectin in end-stage kidney disease patients

Abstract

BACKGROUND: Resistin is a major adipose tissue cytokine implicated in insulin resistance, inflammation and vascular damage. This cytokine is raised in patients with end-stage kidney disease (ESKD) but the relationship between resistin and major clinical outcomes has not been investigated in this population. METHODS: We studied the mutual relationship between resistin and the two major adipokines (adiponectin and leptin) and the interaction between resistin and adiponectin (ADPN) and all-cause and cardiovascular (CV) mortality in a cohort of 231 haemodialysis patients followed up for 57 ± 44 months. RESULTS: Plasma resistin was substantially raised in ESKD patients when compared with healthy subjects (P < 0.001). On univariate analysis, resistin was related inversely to ADPN (r = -0.14, P = 0.04) and directly to C-reactive protein (r = 0.15, P = 0.03), but was largely independent of leptin (r = 0.08, P = 0.24) and the HOMA-IR index (r = -0.04, P = 0.51). During the follow-up, 165 patients died (96 for CV causes). On both univariate (all-cause mortality: P = 0.004; CV mortality P < 0.001) and multivariate (all-cause mortality: P = 0.01; CV mortality P < 0.001) Cox regression analyses, the effect of resistin on study outcomes was closely dependent on ADPN levels. There was a consistent excess risk for all-cause (P = 0.002) and CV mortality (P = 0.003) by plasma resistin (20 ng/mL) in patients in the first ADPN tertile, but no risk excess for these outcomes was apparent in patients in the third tertile. CONCLUSION: This study indicates that resistin predicts death and fatal CV events depending on plasma ADPN levels. These findings underscore the importance of the interaction among adipokines for the prediction of adverse clinical outcomes in ESKD.