Relevance of oxidative and carbonyl stress to long-term uremic complications

Oxidative stress is a disturbance of balance between oxidants and antioxida nt species. The existence of an increased oxidative stress in chronic renal failure is supported by evidence of increased lipid, carbohydrate, and pro tein oxidation products in plasma and cell membrane. Recent studies have im plicated the oxidative stress in the nonenzymatic biochemistry leading to i rreversible protein modifications. Reactive oxygen species may directly alt er proteins with the eventual formation of oxidized amino acids. Alternativ ely, reactive carbonyl compounds formed by the oxidation of carbohydrates a nd lipids may indirectly lead to advanced glycation or lipoxidation of prot eins. Chronic uremia is associated with increased modification of protein c aused by reactive carbonyl compounds derived from bath carbohydrates and li pids. Increased carbonyl modification of proteins subsequently results in t he rise of plasma and tissue contents of advanced glycation end products an d advanced lipoxidation end products, in which the deleterious biological e ffects have been revealed. This article focuses on the irreversible nonenzy matic modification of proteins, which might, at least in part, contribute t o the development of complications associated with chronic renal failure an d long-term dialysis, such as atherosclerosis and dialysis-related amyloido sis.