Receptor for Advanced Glycation End Products in Donor Lungs Is Associated with Primary Graft Dysfunction After Lung Transplantation

• Authors: A. Pelaez, Emory University; Seth Force, Emory University; Anthony Gal, Emory University; David Neujahr, Emory University; A.M. Ramirez, Emory University; P.M. Naik, Emory University; David Quintero, Emory University; A.V. Pileggi, Emory University; Kirk Easley, Emory University; R. Echeverry, Emory University; E. Lawrence, Emory University; David Guidot, Emory University; P.O. Mitchell, Emory University
• Journal Title: American Journal of Transplantation
• Volume: Volume 10, Number 4
• Publisher: Wiley | 2010-04-01, Pages 900-907
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/j.1600-6143.2009.02995.x
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Surgery; Transplantation; Lung transplantation; primary graft dysfunction; receptor for advanced glycation end products; RAGE; reperfusion injury; ALVEOLAR FLUID CLEARANCE; PERFUSED HUMAN LUNGS; MARKER; SURVIVAL; OUTCOMES

Abstract

Development of primary graft dysfunction (PGD) is associated with poor outcomes after transplantation. We hypothesized that Receptor for Advanced Glycation End-products (RAGE) levels in donor lungs is associated with the development of PGD. Furthermore, we hypothesized that RAGE levels would be increased with PGD in recipients after transplantation. We measured RAGE in bronchoalveolar lavage fluid (BALf) from 25 donors and 34 recipients. RAGE was also detected in biopsies (TBBX) from recipients with and without PGD. RAGE levels were significantly higher in donor lungs that subsequently developed sustained PGD vs transplanted lungs that did not display PGD. Donor RAGE level was a predictor of recipient PGD (odds ratio = 1.768 per 0.25 ng/ml increase in donor RAGE level). In addition, RAGE levels remained high at 14 days in those recipients that developed severe graft dysfunction. Recipients may be at higher risk for developing PGD if they receive transplanted organs that have higher levels of soluble RAGE prior to explantation. Moreover, the clinical and pathologic abnormalities associated with PGD post-transplantation are associated with increased RAGE expression. These findings also raise the possibility that targeting the RAGE signaling pathway could be a novel strategy for treatment and/or prevention of PGD.