relationship between advanced glycosylation end products, inflammation and oxidative stress in patients with end-stage renal disease undergoing hemodialysis

Abstract

Controlling systemic proinflammatory and prooxidant effectors is essential for mitigating cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, monitoring these processes is still challenging due to the high uncertainty about their determinants and predictors. Thus, we investigated the relationship between advanced glycosylation end products (AGE), proinflammatory and prooxidant status in ESRD patients undergoing hemodialysis (HD). In addition to nutritional profile and dialysis efficiency, AGE, cytokines, chemokines, C-reactive protein (CRP), total antioxidant capacity (TAC) and antioxidant capacity non-protein (npAC), lipid and protein oxidation were analyzed in blood samples from 49 HD patients. AGE, CRP, cytokines (TNF, IL-6 and IL-10), chemokines (CCL-2, MIP-1α and MIP-1B), protein carbonyl, and malondialdehyde were upregulated, while TAC and npAC were down-regulated in HD patients compared to heath subjects. Dialysis efficiency was reduced, while leukocytes counting, pre- and post-HD urea were increased in patients with higher AGE accumulation. Serum levels of CRP, protein carbonyl, and malondialdehyde and all cytokines and chemokines analyzed were correlated with AGE circulating levels. AGE was inversely correlated with IL-10, TAC and npAC in patients with higher AGE accumulation. AGE exhibited marked predictive value (determination coefficient) to explain CRP, cytokines, chemokines, PCN, MDA, TAC and npAC variability in patients with higher AGE levels. Taken together, our findings provide evidence that ACE accumulation is associated with important proinflammatory and prooxidant effectors in patients with ESRD undergoing hemodialysis. Thus, ACE monitoring may be relevant to predict systemic inflammatory stress and the balance between oxidant and antioxidant status in these patients.