AGEs and cardiovascular diseases in patients with end-stage renal diseases

Cardiovascular disease is the major cause of death in patients with renal insufficiency, accounting for 50% of all deaths in renal replacement therapy patients. Mortality from cardiovascular diseases in these patients is approximately 9% per year, which is about 30 times the risk in the general population. So far, intensive interventions to the general risk factors, such as high levels of low-density lipoprotein -cholesterol or C-reactive protein, have not been successful in improving their cardiovascular outcomes, suggesting that the beneficial effect of risk reduction may be overwhelmed by accumulated risk memorized by long-term exposure to oxidative stress during the progression of renal failure. This irreversible memory effect may be mediated by advanced glycation end products (AGEs), the generation of which has been implicated to be deeply associated with increased oxidative stress. To examine whether circulating AGEs predict future cardiovascular events, a cohort containing 386 (243 male, 142 female) hemodialysis patients was set up. The patients were examined for plasma pentosidine at registration (December 2005) and were followed until March 2010. Patients with high tertile for plasma pentosidine exhibited significantly higher risk for cardiovascular events (hazard risk: 1.74, 95% confidence interval: 1.11 to 2.74, P = .017). Comparisons of the risk of high plasma pentosidine in key subgroups showed that the risk of the high tertile was more prominent in patients with low serum albumin levels. Thus, AGE levels could represent accumulated oxidative stress during the progression of CKD, and their measurements would be useful for stratification of the cardiovascular risks in patients with ESRD.