AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications

Advanced glycation end products (AGEs) may be involved in the pathogenesis of complications of chronic renal failure. Pentosidine, a carbohydrate-deri ved AGE? is considerably elevated in uraemic patients. This compound per se has no biological activities but is highly correlated to the levels of pre cursors of carbonyl compounds, and for this reason is considered a reliable surrogate marker for AGEs. The modification of proteins in uraemia is not limited to AGEs, since advanced lipoxidation end products are also demonstr able in plasma proteins in uraemia. The accumulation of these compounds doe s not seem to be dependent only on the decline of renal function. Carbonyl precursors of AGEs and advanced lipoxidation end products are markedly elev ated in uraemic patients. On this basis, the 'carbonyl stress' theory has b een formulated. This theory holds that increased oxidation of carbohydrates and lipids and/or inadequate detoxification of carbonyl compounds may cont ribute to long-term complications of end-stage renal disease such as dialys is amyloidosis and cardiovascular diseases. Preliminary cross-sectional stu dies in haemodialysis patients seem to indicate that the AGEs and carbonyl stress may be involved in the pathogenesis of alterations in left ventricul ar geometry and function in these patients.