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

Abstract

Advanced glycation end products (AGEs) may be involved in the pathogenesis of complications of chronic renal failure. Pentosidine, a carbohydrate-derived AGE, is considerably elevated in uraemic patients. This compound per se has no biological activities but is highly correlated to the levels of precursors 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 demonstrable in plasma proteins in uraemia. The accumulation of these compounds does not seem to be dependent only on the decline of renal function. Carbonyl precursors of AGEs and advanced lipoxidation end products are markedly elevated in uraemic patients. On this basis, the 'carbonyl stress' theory has been formulated. This theory holds that increased oxidation of carbohydrates and lipids and/or inadequate detoxification of carbonyl compounds may contribute to long-term complications of end-stage renal disease such as dialysis amyloidosis and cardiovascular diseases. Preliminary cross-sectional studies in haemodialysis patients seem to indicate that the AGEs and carbonyl stress may be involved in the pathogenesis of alterations in left ventricular geometry and function in these patients.