A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation.
BACKGROUND
We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research.


METHODS
Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality.


RESULTS
PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p < 0.001 each).


CONCLUSIONS
Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.
Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. rupal.shah@uphs.upenn.edu
Rupal J
RJ
Shah
Scarlett L
SL
Bellamy
A Russell
AR
Localio
Nancy
N
Wickersham
Joshua M
JM
Diamond
Ann
A
Weinacker
Vibha N
VN
Lama
Sangeeta
S
Bhorade
John A
JA
Belperio
Maria
M
Crespo
Ejigayehu
E
Demissie
Steven M
SM
Kawut
Keith M
KM
Wille
David J
DJ
Lederer
James C
JC
Lee
Scott M
SM
Palmer
Jonathan
J
Orens
John
J
Reynolds
Ashish
A
Shah
David S
DS
Wilkes
Lorraine B
LB
Ware
Jason D
JD
Christie
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D055370:Lung Injury / Q000097:blood* / Q000175:diagnosis*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000097:blood* / Q000175:diagnosis*; D011446:Prospective Studies
D015415:Biomarkers