Abstract: Objective To investigate the plasma thrombomodulin (Tm) level and to explore its correlation to inflammatory cytokines and carotid atherosclerosis in maintenance hemodialysis (MHD) patients. Methods A total of 102 stable MHD patients undergoing hemodialysis for at least three months as well as 40 healthy controls were enrolled in the study. Blood levels of Tm, IL-1β, IL-6 and TNF-α were determined by ELISA. Serum levels of ceratinine, triglycerides, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, albumin, hemoglobin and C-reactive protein (CRP) were measured by routine methods. The intima-media thickness (IMT) of bilateral common carotid arteries and atheromatous plaque in carotid arteries were measured by high-resolution ultrasonography. Correlation analyses of Tm with cytokines, atherosclerosis and other parameters were performed. Results Plasma Tm level (16.06 ± 6.68mg/L vs. 5.45 ± 2.14mg/L, t=10.015, P＜0.001), and serum levels of IL-1β (t=6.455, P＜0.001), IL-6 (t=5.650, P＜0.001), TNF-α (t=7.252, P＜0.001) and CRP (t=4.588, P＜0.001) were significantly higher in MHD patients than in healthy controls. The prevalence of atheromatous plaques and the IMT value of carotid arteries increased significantly in MHD patients as compared with those in healthy controls. Plasma Tm level was higher in MHD patients with carotid atherosclerosis than in patients without carotid atherosclerosis (t=7.034, P＜0.001). Tm was positively correlated to IL-1β (r=0.296, P=0.004), IL-6 (r=0.328, P=0.001), TNF-α (r=0.288, P=0.005), CRP (r=0.287, P=0.005), IMT (r=0.585, P=0.003) and carotid atherosclerosis (r=0.588, P＜0.001). Multiple stepwise regression analyses showed that Tm (OR=1.166, 95% CI 1.042～1.305, P＝0.008), IL- 1β (OR=1.005, 95% CI 1.000～1.009, P=0.030), IL-6 (OR=1.025, 95% CI 1.006～1.212, P=0.018), SBP (OR=1.040,95% CI 1.010～1.219, P=0.023) and age (OR=1.036, 95% CI 1.467～2.009, P=0.019) were the independent risk factors for carotid atherosclerosis in MHD patients. Conclusion Plasma Tm level is significantly higher in MHD patients and is positively correlated with IL-1β, IL-6, TNF-α, CRP, and carotid atherosclerosis, indicating that Tm is an independent risk factor for carotid atherosclerosis in MHD patients. Plasma Tm may be used as a marker to evaluate endothelial damage.

Key words: Hemodialysis, Thrombomodulin, Cytokine, Atherosclerosis