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PLoS One. 2014 Mar 27;9(3):e93460. doi: 10.1371/journal.pone.0093460. eCollection 2014.

Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery.

Author information

1
Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
2
Department of Cardiac Surgery, University of Münster, Germany.
3
Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.
4
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
5
Center for Critical Care Nephrology, CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pennsylvania, United States of America.

Abstract

BACKGROUND:

Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients.

METHODS:

We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge.

RESULTS:

26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1-3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery.

CONCLUSIONS:

Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery.

CLINICAL TRIAL REGISTRATION INFORMATION:

www.germanctr.de/, DRKS-ID: DRKS00005062.

PMID:
24675717
PMCID:
PMC3968141
DOI:
10.1371/journal.pone.0093460
[Indexed for MEDLINE]
Free PMC Article

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