Plasma Receptor for Advanced Glycation End-products Predicts Duration of ICU Stay and Mechanical Ventilation in Patients After Lung Transplantation

Background: Primary graft dysfunction, formerly termed reperfusion pulmonary edema, is the leading cause of short-term complications after lung transplantation. New evidence shows that alveolar type I epithelial cells play an active role in alveolar fluid transport and are therefore presumed to be critical in the absorption of pulmonary edema. We tested the potential relevance of a novel marker of alveolar type I cell injury, the receptor for advanced glycation end-products (RAGE), to short-term outcomes of lung transplantation. Methods: The study was a prospective, observational cohort study of 20 patients undergoing single lung, bilateral lung or combined heart-lung transplantation. Plasma biomarkers were measured 4 hours after allograft reperfusion. Results: Higher plasma RAGE levels were associated with a longer duration of mechanical ventilation and longer intensive care unit length of stay, in contrast to markers of alveolar type II cell injury, endothelial injury and acute inflammation. Specifically, for every doubling in plasma RAGE levels, the duration of mechanical ventilation increased on average by 26 hours, adjusting for ischemia time (95% confidence interval [CI] 7.4 to 44.7 hours, p = 0.01). Likewise, for every doubling of plasma RAGE levels, intensive care unit length of stay increased on average by 1.8 days, again adjusting for ischemia time (95% CI 0.13 to 3.45 days p = 0.04). In contrast, the clinical diagnosis of primary graft dysfunction was not as predictive of these short-term outcomes. Conclusions: Higher levels of plasma RAGE measured shortly after reperfusion predicted poor short-term outcomes from lung transplantation. Elevated plasma RAGE levels may have both pathogenetic and prognostic value in patients after lung transplantation.