701: Soluble P-Selectin and the Risk of Primary Graft Dysfunction after Lung Transplantation

Abstract

Purpose:The Receptor for Advanced Glycation End-Products (RAGE) is an important marker of lung epithelial injury, and may be associated with impaired alveolar fluid clearance. Blockade of RAGE may attenuate lung injury in animal models. We hypothesized that PGD patients would have higher RAGE levels in plasma than non-PGD patients. Methods and Materials: Prospective, multicenter cohort study. We measured plasma levels of RAGE at 6 and 24 hours following allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was Grade 3 PGD (PaO 2 /FiO 2 Ͻ200 with alveolar infiltrates) at 72 hours after transplantation. Multivariable logistic regression was used to adjust for confounding. Results: Patients who developed PGD had higher levels of RAGE than patients without PGD in both the immediate post-transplantation period (mean 21,246 Ϯ 27,761 pg/mL in PGD vs 12,394 Ϯ 14,767 in those without, pϭ0.005) and the 24 hour time period (12,240 Ϯ 26,505 in those with PGD versus 4265 Ϯ 10,122 in those without, pϽ0.001). RAGE levels at 6 hours were significantly associated with the use of cardiopulmonary bypass. Multivariable analyses indicated that the relationship between 24 hour levels of RAGE and PGD was independent of clinical variables (Adjusted OR for each 10,000 pg/mL ϭ 1.23 (95%CI: 1.05, 1.45; pϽ0.01); whereas levels were attenuated by both the right heart pressures and use of CPB at the 6 hour time point. Conclusions: Elevated plasma levels of RAGE are associated with PGD following lung transplantation. In addition, use of cardiopulmonary bypass was associated with higher RAGE levels, suggesting either alveolar injury that is caused by cardiopulmonary bypass, or, alternately, systemic endothelial production of RAGE in the setting of bypass use.