Institutional members access full text with Ovid®

Share this article on:

Acute kidney injury is associated with early cytokine changes after trauma

Bihorac, Azra MS, MD; Baslanti, Tezcan Ozrazgat PhD; Cuenca, Alex G. MD, PhD; Hobson, Charles E. MD, MHA; Ang, Darwin MD, PhD; Efron, Philip A. MD; Maier, Ronald V. MD; Moore, Frederick A. MD; Moldawer, Lyle L. PhD

Journal of Trauma and Acute Care Surgery: April 2013 - Volume 74 - Issue 4 - p 1005–1013
doi: 10.1097/TA.0b013e31828586ec
Original Articles

BACKGROUND Acute kidney injury (AKI) occurs in 26% of trauma patients and is associated with increased mortality and risk for nosocomial infections (NCIs). We compared serial plasma cytokine levels in patients with posttraumatic AKI to determine whether the early cytokine changes are associated with the occurrence of AKI and NCI.

METHODS We performed a secondary analysis of the Inflammation and the Host Response to Injury database to include adult blunt trauma patients who had available plasma proteomic analyses. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification, which requires a 50% increase in serum creatinine. The association among AKI, NCI, and plasma cytokines was analyzed using a mixed model analyses and logistic regression.

RESULTS Among 147 patients in the cohort, prevalence of NCI was 73% and 52% for patients with and without AKI, respectively. In mixed model analyses adjusted for clinical factors, AKI patients developed significant early increase in IL-1ra, IL-8, MCP1, and IL-6; early decrease in sTNFR2; and late decrease in IL-1ra, IL-4, and IL-6 concentrations, compared with patients without AKI and regardless of NCI. The change in cytokine pattern differed for sIL1R2, CXCL1, and MIP1β, depending on the occurrence of NCI. Patients with AKI and NCI had lower early and late sIL1R2 and higher early and late CXCL1 and MIP1β levels. Within the first 24 hours of injury, adding plasma levels of IL-1ra, IL-8, MCP1, IL-6, and sTNFR2 to clinical parameters of injury severity provided a predictive model for AKI superior to clinical model only (p < 0.001).

CONCLUSION AKI trauma patients exhibit simultaneous changes in proinflammatory and anti-inflammatory serial plasma cytokine levels. The predictive model for AKI that combines plasma cytokine levels with clinical data within 24 hours of injury requires further prospective validation in larger studies.

LEVEL OF EVIDENCE Prognostic study, level III.

Supplemental digital content is available in the text.

From the Division of Critical Care Medicine (A.B. T.O.B.), Department of Anesthesiology, and Department of Surgery (A.G.C., D.A., P.A.E., F.A.M., L.L.M.), University of Florida; Department of Surgery (C.E.H.), Malcom Randall VA Medical Center, Gainesville, Florida; and Department of Surgery (R.V.M.), Harborview Medical Center, University of Washington School of Medicine, Seattle, Washington.

Submitted: November 6, 2012, Revised: December 17, 2012, Accepted: December 19, 2012.

The preliminary report of this work was presented as an oral presentation at the 32nd Annual Meeting of the Surgical Infection Society.

The work represents a secondary use of this public database, and although the finished article has been seen by the leadership of the Glue Grant, the conclusions and discussion are the authors’ and do not necessarily represent the views of the Glue Grant, Massachusetts General Hospital, or the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Address for reprints: Azra Bihorac, MS, MD, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Rd, M-509 Box 100254, Gainesville, FL 32610-0254; email:

© 2013 Lippincott Williams & Wilkins, Inc.