Why hemodialysis patients are in a prooxidant state? What could be done tocorrect the pro/antioxidant imbalance

Oxidative stress which results from an imbalance between reactive oxygen sp ecies production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pat hologies such as accelerated atherosclerosis, amyloidosis and anemia. In or der to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be respon sible for the imbalance between pro- and antioxidative mechanisms. The infl ammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species cont ributing by this way to worsen the prooxidant status of uremic patients. Tw o factors largely contribute to the stimulation of the NADPH oxidase: hemor eactivity of the mem bra ne and trace amounts of endotoxins. The antioxidan t system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant syst em mainly by losses of (a) hydrophilic unbound small-molecular-weight subst ances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compo unds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatib ility of the dialysis system mainly by using a dialyzer with low hemoreacti vity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achi eved by oral or perdialytic supplementation. Vitamin E could be bound on di alyzer membrane. Alternatively, hemolipodialysis consists in loading HD pat ients with vitamin C or E via an ancillary circuit made of vitamin E-rich l iposomes. The presence of liposomes could also facilitate the removal of hy drophobic prooxidative substances. Copyright (C) 2000 S. Karger AG. Basel.