T. Miyata et al., Alterations in nonenzymatic biochemistry in uremia: Origin and significance of "carbonyl stress" in long-term uremic complications, KIDNEY INT, 55(2), 1999, pp. 389-399
Advanced glycation end products (AGEs), formed during Maillard or browning
reactions by nonenzymatic glycation and oxidation (glycoxidation) of protei
ns, have been implicated in the pathogenesis of several diseases, including
diabetes and uremia. AGEs, such as pentosidine and carboxymethyllysine, ar
e markedly elevated in both plasma proteins and skin collagen of uremic pat
ients, irrespective of the presence of diabetes. The increased chemical mod
ification of proteins is not limited to AGEs, because increased levels of a
dvanced lipoxidation end products (ALEs), such as malondialdehydelysine, ar
e also detected in plasma proteins in uremia. The accumulation of AGEs and
ALEs in uremic plasma proteins is not correlated with increased blood gluco
se or triglycerides, nor is it determined by a decreased removal of chemica
lly modified proteins by glomerular filtration. It more likely results from
increased plasma concentrations of small, reactive carbonyl precursors of
AGEs and ALEs, such as glyoxal, methylglyoxal, 3-deoxyglucosone, dehydroasc
orbate, and malondialdehyde. Thus, uremia may be described as a state of ca
rbonyl overload or "carbonyl stress" resulting from either increased oxidat
ion of carbohydrates and lipids (oxidative stress) or inadequate detoxifica
tion or inactivation of reactive carbonyl compounds derived from both carbo
hydrates and lipids by oxidative and nonoxidative chemistry. Carbonyl stres
s in uremia may contribute to the long-term complications associated with c
hronic renal failure and dialysis, such as dialysis-related amyloidosis and
accelerated atherosclerosis. The increased levels of AGEs and ALEs in urem
ic blood and tissue proteins suggest a broad derangement in the nonenzymati
c biochemistry of both carbohydrates and lipids.