Advanced glycation end products and mortality in hemodialysis patients

Background. Advanced glycation and oxidation end products (AGEs) cause oxidative stress and trigger cytokine driven inflammatory reactions in vitro. The net effects on markers of inflammation and acute phase proteins in vivo as well as their influence on survival in hemodialysis patients are unknown. Methods. We conducted a cross-sectional study in 312 stable hemodialysis patients and analyzed the interrelationships of AGEs an C-reactive protein (CRP) and their predictive effect on all-cause as well as cardiovascular mortality. Mortality was monitored prospectively over a period of 32 months. AGEs were determined by measuring total serum fluorescent AGEs (AGE-fl) and N-epsilon-(carboxymethyl)-lysine (CML). Results. The levels of AGE-fl, CML and CRP were 3.2-,3.8- and 10-fold higher as compared to healthy controls. AGE-fl and CML levels correlated significantly with each other but not with CRP or serum albumin. Patients with high (above median values) AGE-fl or CML levels (109 x 10(3) AU and 1.4 mug/mL, respectively) had a significant better survival than those with low (below median values) AGE-fl or CML levels. Patients with high CRP levels (above 7.7 mg/L = median value) had a better survival than those with low CRP (below median value) when AGE-fl or CML levels were high in parallel. Conclusions. In contrast to in vitro data and to current hypotheses. the presence of high serum AGEs, as measured by AGE-fl and CML, were not linked to increased mortality. Statistically, high serum AGEs partly overcame the negative impact of the acute phase response on mortality in hemodialysis patients. Whether the benefit of high serum AGEs is an epiphenomenon or reflects a better nutritional support needs further studies.