Why Hemodialysis Patients Are in a Prooxidant State? What Could Be Done to Correct the Pro/Antioxidant Imbalance

Abstract

Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.

Effect of hemodialysis on traditional and innovative cardiac markers

“…However, we have also observed a significant and unpredictable increase post-HD, which was not accompanied by biochemical or clinical symptoms of skeletal muscle and myocardial ischemia. This is consistent with the conclusion that HD-induced oxidative stress and damage are commonplace and the IMA increase might be attributable to the hemobioincompatibility of the dialysis system that plays a critical role in the production of free oxygen radical species (56). Moreover, since IMA values rise within minutes after the onset of ischemia, remain elevated for 6 to 12 hours, and return to baseline within 24 hr (57), our findings support the hypothesis that baseline pre-HD values might be used to predict long-term mortality and morbidity, whereas the heterogeneous and unpredictable increase post-HD would not be useful for the diagnosis of an ACS occurred during or immediately after HD.…”

Inflammatory Syndrome in Patients on Hemodialysis

“…Loss of some antioxidants, such as carnitine, during HD may contribute to this disorder (70). There is a clear interconnection between inflammation and oxidative stress in HD (71,72).…”

Influence of Cocoa Flavanols and Procyanidins on Free Radical‐induced Human Erythrocyte Hemolysis

“…Excessive oxidative damage to cellular membranes may contribute to the development of many degenerative diseases, including certain cancers and cardiovascular diseases (Cooke et al 2003, Hensley et al 2000, Kris-Etherton et al 2004, Morena et al 2000, Morton et al 2000. Erythrocytes are especially susceptible to oxidation due to their high content of polyunsaturated lipids, their rich oxygen supply and the presence of transition metals such as iron and copper (DelmasBeauvieux et al 1995, Mennen et al 2004.…”