Early release of soluble receptor for advanced glycation endproducts after severe trauma in humans.
BACKGROUND
The receptor for advanced glycation endproducts (RAGE) recognizes a variety of ligands that play an important role in the posttraumatic inflammatory response. However, whether soluble RAGE (sRAGE) is released early after trauma hemorrhage in humans and whether such a release is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of this study.


METHODS
One hundred sixty-eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level I Trauma center. Blood was drawn within 10 minutes of arrival to the emergency department before the administration of any fluid resuscitation. sRAGE, tumor necrosis factor-alpha, interleukin-6, von Willebrand factor, angiopoietin-2, prothrombin time, prothrombin fragments 1 + 2, soluble thrombomodulin, protein C, plasminogen activator inhibitor-1, and d-dimers (fibrin degradation products) were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared with outcome measures obtained from the electronic medical record and trauma registry.


RESULTS
Plasma levels of sRAGE were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, early posttraumatic coagulopathy and hyperfibrinolysis, and endothelial cell activation (angiopoietin-1 and complement). Furthermore, we found that there was a significant relationship between plasma levels of sRAGE and the development of acute renal failure. This relationship was not quite significant for patients who developed acute lung injury (p = 0.11), although patients with <26 ventilator-free days had significantly higher plasma levels of sRAGE than those with >26 ventilator-free days. Finally, there was no relationship between plasma levels of sRAGE and mortality rate in trauma patients.


CONCLUSIONS
The results of this study demonstrate that the release of sRAGE in the bloodstream of trauma patients requires severe injury and is associated with coagulation abnormalities and endothelial cell and complement activation.
. Department of Surgery, Ward 3A, San Francisco General Hospital, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110, USA. mcohen@sfghsurg.ucsf.edu
Mitchell J
MJ
Cohen
Michel
M
Carles
Karim
K
Brohi
Carolyn S
CS
Calfee
Pamela
P
Rahn
Mariah S
MS
Call
Brian B
BB
Chesebro
Michael A
MA
West
Jean-François
JF
Pittet
D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood; D001774:Blood Chemical Analysis; D001778:Blood Coagulation Disorders / Q000097:blood; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006470:Hemorrhage / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D015601:Injury Severity Score; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012042:Registries; D018709:Statistics, Nonparametric; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000097:blood*
D042683:Angiopoietin-1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003165:Complement System Proteins