Receptor for advanced glycation end products in donor lungs is associated with primary graft dysfunction after lung transplantation.
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 (transbronchial biopsy) from recipients with and without PGD. RAGE levels were significantly higher in donor lungs that subsequently developed sustained PGD versus 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 for 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 posttransplantation 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.
Pelaez
A
A
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
Force
S D
SD
McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.|Division of Cardiothoracic Surgery, Emory University, Atlanta, GA.
Gal
A A
AA
Department of Pathology and Laboratory Medicine, Emory University Hospital.
Neujahr
D C
DC
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
Ramirez
A M
AM
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
Naik
P M
PM
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
Quintero
D A
DA
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
Pileggi
A V
AV
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
Easley
K A
KA
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
Echeverry
R
R
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
Lawrence
E C
EC
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
Guidot
D M
DM
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
Mitchell
P O
PO
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
D001706:Biopsy; D006084:Graft Rejection; D006801:Humans; D016040:Lung Transplantation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D014019:Tissue Donors
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic