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Critical Care

Open Access

Urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery

  • A Zarbock1,
  • M Meersch1,
  • C Schmidt1,
  • S Martens1,
  • J Rossaint1,
  • K Singbartl2,
  • D Görlich1,
  • J Kellum3 and
  • H Van Aken1
Critical Care201418(Suppl 1):P381

Published: 17 March 2014


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 AKI, could predict AKI in cardiac surgery patients.


We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass. 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.


Twenty-six patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1 to 3 days after cardiopulmonary bypass. In contrast, urine concentration of [TIMP-2] × [IGFBP7] rose from a mean of0.49 (0.24) at baseline to 1.51 (0.57) 4 hours after cardiopulmonary bypass in patients who developed AKI. The maximum urinary [T|MP-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.


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

Authors’ Affiliations

University of Münster, Germany
Penn State College of Medicine Hershey, USA
University of Pittsburgh, USA


© Zarbock et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.