Alterations in non-enzymatic biochemistry in uremia: carbonyl stress

Abstract

Proteins are modified with advanced glycation end products (AGEs) during normal process of aging. This process is markedly accelerated in diabetes and contribute to the development of diabetic complications. These discoveries have opened new avenues for research on uremic toxicity. AGEs accumulate markedly in uremic patients: observed serum levels of AGEs, such as pentosidine and carboxymethyllysine (CML), were indeed elevated several times above those of diabetic patients and appeared unrelated to elevated glucose levels. As pentosidine and CML are mainly linked to albumin in the serum, its accumulation cannot be attributed to a decreased removal by glomerular filtration. Recently, gathered evidence has suggested that, in uremia, the increased carbonyl compounds, derived from both oxidative and non-oxidative processes involving both carbohydrates and lipids, modify proteins by not only glycoxidation reaction (leading to augument AGE production) but also lipoxidation reaction (leading to augument advanced lipidation end product, ALE, production). Thus, uremia might be a state of carbonyl overload (“carbonyl stress”) with potentially damaging proteins. Carbonyl stress in uremia appears relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and accelerated atherosclerosis. The increased levels of AGEs and ALEs in blood and tissues in uremic patients may betray a broad derangement in non-enzymatic biochemistry.