Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery Following Cardiac Surgery

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

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / urine*
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers / urine
  • Cardiopulmonary Bypass / adverse effects*
  • Creatinine / blood
  • Female
  • Gene Expression
  • Heart Failure / complications
  • Heart Failure / surgery*
  • Heart Failure / urine
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Male
  • Postoperative Complications*
  • Prognosis
  • ROC Curve
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / urine*

Substances

  • Biomarkers
  • Insulin-Like Growth Factor Binding Proteins
  • TIMP2 protein, human
  • insulin-like growth factor binding protein-related protein 1
  • Tissue Inhibitor of Metalloproteinase-2
  • Creatinine

Grant support

The work was supported by the German Research Foundation (ZA428/6-1 to A.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.