Hemodialysis Impairs Endothelial Function via Oxidative Stress

Abstract

Background —Patients who undergo hemodialysis experience accelerated atherosclerosis and premature death. Recent evidence suggests that endothelial dysfunction proceeds to and exacerbates atherosclerosis. It remains unknown whether hemodialysis per se causes endothelial dysfunction. Methods and Results —We evaluated endothelial function estimated by flow-mediated vasodilation during reactive hyperemia using high-resolution ultrasound Doppler echocardiography before and after a single session in patients on maintenance hemodialysis. Several studies have shown that the imbalance between pro-oxidant and antioxidant activities in hemodialyzed patients results in high oxidative stress, which causes lipid peroxidation and endothelial injury. Accordingly, we investigated the effects of antioxidative modification during hemodialysis on endothelial function using a vitamin E–coated cellulose membrane dialyzer. Nonspecific endothelium-independent vasodilation was measured after administration of a sublingual glyceryl trinitrate spray (0.3 mg). A single session of hemodialysis by noncoated dialyzer impaired flow-mediated vasodilation ( P <0.05) associated with increased plasma levels of oxidized LDL ( P <0.05), an index of oxidative stress. Hemodialysis by vitamin E–coated membrane prevented dialysis-induced endothelial dysfunction and increases in oxidized LDL. Plasma levels of oxidized LDL were inversely correlated with the magnitudes of flow-mediated vasodilation ( r =−0.53, P < 0.001). Hemodialysis by noncoated or vitamin E–coated membrane did not affect glyceryl trinitrate–induced endothelium-independent vasodilation. Conclusions —Our findings indicate that hemodialysis per se impairs endothelial function, possibly by increasing oxidative stress.