Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction.
BACKGROUND
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. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD.


OBJECTIVE
To test the association of soluble RAGE (sRAGE) levels with PGD in a prospective, multicenter cohort study.


METHODS
We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) within the first 72 hours after transplantation.


RESULTS
Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearman's rho = 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02).


CONCLUSIONS
Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.
Christie
Jason D
JD
Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. jchristi@mail.med.upenn.edu
Shah
Chirag V
CV
Kawut
Steven M
SM
Mangalmurti
Nilam
N
Lederer
David J
DJ
Sonett
Joshua R
JR
Ahya
Vivek N
VN
Palmer
Scott M
SM
Wille
Keith
K
Lama
Vibha
V
Shah
Pali D
PD
Shah
Ashish
A
Weinacker
Ann
A
Deutschman
Clifford S
CS
Kohl
Benjamin A
BA
Demissie
Ejigayehu
E
Bellamy
Scarlett
S
Ware
Lorraine B
LB
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016913:Blood Component Transfusion; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000097:blood*; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D013997:Time Factors
D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic