First-Days Reduction of Plasma and Skin Advanced Glycation End Products is Related to Outcome in Septic Patients

Background: Advanced glycation end products (AGEs) are a result of nonenzymatic glycation of proteins and lipids, which can attach to either their cell surface receptor (RAGE) or its soluble form (sRAGE). Evidence exists for the implication of AGE-RAGE axis in sepsis, but data are still insufficient and conflicting. We aimed to analyze the kinetics of plasma and skin AGEs and sRAGE during sepsis, and their association with outcome in septic patients. Methods: We performed a prospective observational study. We enrolled 90 consecutive patients with severe sepsis or septic shock, within the first 24 h of Intensive Care Unit admission. During the first 5 days of sepsis, we measured plasma autofluorescence (PAF) and skin autofluorescence (SAF) as surrogates of circulating and skin AGEs, respectively. sRAGE was measured on days 1, 3, and 5. Delta values were defined as the difference between the PAF, SAF, or sRAGE on a specific day and the value on day 1. Results: 28-day mortality was 18%. Bivariate analysis found that Delta PAF(3-1,)Delta PAF(4-1), Delta PAF(5-1), and Delta SAF(5-1)were significantly associated with 28-day mortality. Additionally, sRAGE(1)was inversely correlated to Delta PAF(4-1)(r = -0.250,P = 0.019) and Delta PAF(5-1)(r = -0.246,P = 0.024), and significantly associated with 28-day mortality. In an adjusted multivariate logistic regression analysis, Delta PAF(2-1), Delta PAF(3-1), Delta PAF(4-1), Delta PAF(5-1), and Delta SAF(5-1)were associated with 28-day mortality. Conclusions: Kinetics of plasma and skin AGEs during the first days of sepsis are independently associated with mortality, where a decrease of plasma and skin AGEs are related to higher mortality.