(870) - Elevated Plasma PAI-1 Levels in the Donor Are Associated with the Development of Primary Graft Dysfunction in Lung Transplant Recipients

Abstract

Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality following lung transplantation. Early prediction of PGD would allow earlier interventions and better patient outcomes. Clinical factors, such as cigarette smoking, have been identified in the donor that increase the risk of PGD. Biological factors may also contribute. Elevated recipient plasma levels of plasminogen activator inhibitor-1 (PAI-1) and the receptor for advanced glycation end-products (RAGE) are known to be associated with a higher risk of developing PGD. However, these and other biomarkers in the donor plasma have not yet been shown to contribute to the risk of PGD. We tested the hypothesis that elevated donor plasma levels of PAI-1 and RAGE would be associated with recipient PGD. We carried out a prospective unmatched case control study for double lung transplants between June 2014 and September 2015. The primary outcome was donor plasma levels of PAI-1 and RAGE prior to organ recovery. We compared 12 recipients who developed PGD Grade 2 or 3 by ISHLT criteria within 72 hours postoperatively, with 13 recipients who did not. PaO2/FiO2 was measured concurrent with chest radiograph upon ICU arrival, 24, 48 and 72 hours postoperatively. Plasma biomarker levels in duplicate were compared between cases and controls using the Wilcoxon rank-sum test. Donor plasma levels of PAI-1 were significantly higher in those recipients who developed grade 2 or 3 PGD compared to those who did not (p=0.03) (Table). Plasma levels of PAI-1 remained significantly higher at 24 hours in the recipients that developed PGD compared to the non-PGD group (11.57 vs 1.95 ng/mL, p<0.001). RAGE was not statistically different between groups. Donor systemic inflammatory responses as reflected by significantly elevated plasma levels of PAI-1 may contribute to the risk of developing PGD. Rapid biomarker assessment may assist in donor lung selection and early risk stratification.Tabled 1Median donor plasma levels of PAI-1 and RAGE in cases versus controlsDonor Plasma BiomarkerCases (n=12) Median (IQR)Controls (n=13) Median (IQR)P valuePAI-1 (ng/mL)2.73 (2.07-5.51)1.39 (1.07-2.89)0.03RAGE (pg/mL)1061 (475 - 1930)679 (400-747)0.11IQR, interquartile range; PAI-1, plasminogen activator inhibitor-1; RAGE, receptor for advanced glycation end-products. Open table in a new tab