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

Melanie Meersch, Christoph Schmidt, Hugo Van Aken, Sven Martens, Jan Rossaint, Kai Singbartl, Dennis Görlich, John A. Kellum, Alexander Zarbock

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199 Scopus citations

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.

Original languageEnglish (US)
Article numbere93460
JournalPloS one
Volume9
Issue number3
DOIs
StatePublished - Mar 27 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Meersch, M., Schmidt, C., Van Aken, H., Martens, S., Rossaint, J., Singbartl, K., Görlich, D., Kellum, J. A., & Zarbock, A. (2014). Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PloS one, 9(3), [e93460]. https://doi.org/10.1371/journal.pone.0093460