Decoy Receptor 3, a Novel Inflammatory Marker, and Mortality in Hemodialysis Patients

Abstract

Inflammation is closely associated with cardiovascular disease, the leading cause of mortality in patients with CKD. Serum decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. CKD patients have higher levels of DcR3 than the general population, but whether DcR3 predicts mortality in CKD patients on hemodialysis has not been explored. DcR3 levels were measured in 316 prevalent hemodialysis patients who were followed up from November 1, 2004, to June 30, 2009, for cardiovascular and all-cause mortality. The baseline DcR3 concentration showed a strong positive correlation with inflammatory markers including high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). During a follow-up period of 54 months, 90 patients died (34 cardiovascular deaths). Kaplan-Meier survival analysis showed higher cardiovascular and all-cause mortality in patients with higher DcR3 levels. The hazard ratios (95% confidence intervals) of the highest versus lowest tertiles of DcR3 were 2.8 (1.1-7.3; P for trend=0.04) for cardiovascular mortality and 2.1 (1.1-3.7; P for trend=0.02) for all-cause mortality, respectively. Based on the minimal increase in the area under the receiver operating characteristic curve from 0.79 to 0.80, the addition of DcR3 to established risk factors including VCAM-1, albumin, and IL-6 does not improve the prediction of mortality. Higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in CKD patients on hemodialysis.