AUTOXIDATION PRODUCTS OF BOTH CARBOHYDRATES AND LIPIDS ARE INCREASED IN UREMIC PLASMA - IS THERE OXIDATIVE STRESS IN UREMIA

Background. Advanced glycation end products (ACEs), formed by non-enzy matic glycation anti oxidation (glycoxidation) reactions. have been im plicated in the pathogenesis oi several diseases, including normoglyce mic uremia. AGE research in uremia has focused Un the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recen t studies, however, have demonstrated that one AGE, the glycoxidation product carbohydrates carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fat ty acids in vitro. raising the possibility that both carbohydrate and lipid autoxidation might br: increased in uremia. Methods. To address this hypothesis. we applied gas chromatography-mass spectrometry and h igh performance: liquid chromatography to measure protein adducts form ed in uremic plasma reactions between carbonyl compounds and protein a mino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carton-ls. and CML originating possibly from both sources. Results. All three adduct s were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with; fructoselysine levels and were similar in diabetic and non-diabetic patients on hemod ialysis. indicating that their increase was not driven by glucose. Pen tosidine and MDA-lysine were also increased in plasma to the same exte nt in diabetic and non-diabetic hemodialysis patients. Statistical ana lysis indicated that plasma levels of CML correlated weakly (P < 0.05) with those uf pentosidine and MDA-lysine, but that pentosidine and MD A-lysine: varied independently (P > 0.5). Conclusions. These data sugg est th;tt the increased levels of AGEs in blood. and probably in tissu es. reported in uremia implicate a broad derangement in non-enzymatic biochemistry; involving alterations in autoxidation of both carbohydra tes and lipids.