What we know about oxidative stress in patients with chronic kidney disease on dialysis--clinical effects, potential treatment, and prevention.

Patients with chronic kidney disease (CKD) experience accelerated atherosclerosis leading to excessive cardiovascular death. This cannot be fully explained by traditional cardiovascular risk factors. Oxidative stress is currently receiving attention as an important pathogenetic mediator of tissue damage. Oxidative stress is highly prevalent in patients with CKD. Increased prooxidant activity (age, diabetes, hypertension, inflammation, incompatibility of dialysis membranes, and solutions) goes together with reduced antioxidant defense (reduced activity of the glutathione system, low levels of vitamin E, C). Oxidative stress has been linked to several surrogate markers of atherosclerosis in patients with CKD, such as endothelial dysfunction and intima-media thickness. However, large epidemiological studies testing hard endpoints are lacking. Oxidative stress may also influence response to erythropoiesis-stimulating agents. Among possible therapeutic approaches, the use of vitamin E seems to be the most promising. Given orally, it has been shown to significantly improve cardiovascular outcomes in a relatively small clinical trial. When bonded to biocompatible dialysis membranes, it may be effective in improving erythropoiesis-stimulating agents' responsiveness. Similarly, vitamin C may be effective in reducing cardiovascular events in haemodialysis patients. Further well-designed, randomized controlled clinical trials with antioxidants are required to establish their potential to make a substantive difference in clinical practice.