Soluble TWEAK and Cardiovascular Morbidity and Mortality in Chronic Kidney Disease Patients

Introduction: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in chronic kidney patients (CKD). The aim of this study was to demonstrate the role of soluble tumor necrosis factor (TNF) weak inducer of apoptosis (sTWEAK) as a marker of cardiovascular morbidity and mortality in CKD patients.Methods: The study included 75 CKD patients classified according to eGFR into three groups; group-1 included 15 patients with stage-1 CKD, group-2 included 30 patients with stage-2 and stage-3 CKD, and group-3 included 30 patients with stage-4 and stage-5 CKD. The three groups were compared to 20 matched controls. Interleukin-6 (IL-6) and sTWEAK were measured using ELISA and chemiluminescent techniques respectively. Carotid intima-media thickness (IMT) was also measured.Results: We found that IL-6 showed significant difference between patient groups and controls, being highest in stage 4 and 5 CKD patients and lowest in controls. Soluble TWEAK showed significant difference between patient groups and controls, being lowest in stage 4 and 5 CKD patients and highest in controls. Soluble TWEAK level showed significant negative correlation with IL-6 (r = -0.68; P<0.01) and carotid IMT (r = -0.95; P<0.01). After two years follow up, nine out of 75 CKD patients developed ischemic heart disease (IHD). Two patients developed cerebrovascular stroke and another patient developed peripheral arterial disease. These patients had significantly lower levels of sTWEAK at baseline compared to other patients (160.5± 60.2 versus 274.8±90 pg/mL; P < 0.05).Conclusion: Soluble TWEAK can be a novel biomarker of atherosclerosis and endothelial dysfunction as well as cardiovascular outcome in CKD patients