title: Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery?
abstract: BACKGROUND
  Postoperative acute kidney injury (AKI) is a frequently observed complication after on-pump cardiac surgery (CS) and is associated with adverse patient outcomes. Early identification of patients at risk is essential for the prevention of AKI after CS. In this study, we analysed whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) combined with urine insulin-like growth factor binding protein 7 (IGFBP-7) ([TIMP-2] × [IGFBP-7]) is an adequate diagnostic test to identify early AKI after on-pump CS.
  
  
  METHODS
  In 42 patients undergoing coronary artery bypass graft surgery, we surveyed individual risk factors for AKI and defined AKI by applying the Kidney Disease: Improving Global Outcomes (KDIGO) classification during the day of surgery and the following 2 days after surgery. Concentrations of urinary TIMP-2 multiplied by IGFBP-7 were recorded at four time points: at baseline pre-surgery, at the end of surgery, 4 hours after cardiopulmonary bypass (CPB) and at 8:00 AM on the first postoperative day.
  
  
  RESULTS
  In total, 38% of the patients experienced AKI. The results showed a median baseline [TIMP-2] × [IGFBP-7] concentration of 0.3 (ng/ml)(2)/1,000, decreasing at the end of surgery and then increasing at the next measurement point 4 hours after CPB and further on the first postoperative day. On the first postoperative day, patients with AKI had significantly higher concentrations of [TIMP-2] × [IGFBP-7]. On the day of surgery, the concentration did not significantly differ between patients classified as KDIGO 0 or KDIGO 1 or 2. Previously published cutoff points of 0.3 and 2 were not confirmed in our study cohort.
  
  
  CONCLUSIONS
  [TIMP-2] × [IGFBP-7] concentration can be used as a diagnostic test to identify patients at increased risk of AKI after CS on the first postoperative day. At earlier time points, no significant difference in [TIMP-2] × [IGFBP-7] concentration was found between patients classified as KDIGO 0 or KDIGO 1 or 2.
  
  
  BACKGROUND
  German Clinical Trials Register (DRKS) DRKS00005457. Registered 26 November 2013.
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. anna.wetz@med.uni-goettingen.de.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Wetz
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. e.richardt@stud.uni-goettingen.de.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Richardt
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. saskia.wand@med.uni-goettingen.de.
authors.forename: Saskia
authors.initials: S
authors.lastname: Wand
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. nkunze@gwdg.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Kunze
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. hschotola@med.uni-goettingen.de.
authors.forename: Hanna
authors.initials: H
authors.lastname: Schotola
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. mquintel@gwdg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Quintel
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. abraeue@gwdg.de.
authors.forename: Anselm
authors.initials: A
authors.lastname: Bräuer
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany. omoerer@gwdg.de.
authors.forename: Onnen
authors.initials: O
authors.lastname: Moerer
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D006348:Cardiac Surgical Procedures; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2