title: TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients.
abstract: BACKGROUND
  Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI.
  
  
  METHODS
  We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2-3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement.
  
  
  RESULTS
  A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76-0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery).
  
  
  CONCLUSIONS
  For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance.
  
  
  METHODS
  Prognostic study, level I.
authors.affiliation: From the Departments of Emergency Medicine, Anesthesiology, and Internal Medicine (K.J.G.), Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, Michigan; Department of Anesthesia (A.D.S.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine (L.S.C.), Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, Washington, District of Columbia; Department of Anesthesiology (A.B), University of Florida, Gainesville, Florida; Center for Critical Care Nephrology (A.A.-K., J.A.K.), Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Pulmonary and Critical Care Medicine (K.K.), Mayo Clinic, Rochester, Minnesota; Department of Surgery (M.L.), University of Maryland School of Maryland, Baltimore, Maryland; and Statistical Consultant (J.S., M.G.W.), Carlsbad, California.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Gunnerson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shaw
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Khafaji
authors.forename: Kianoush
authors.initials: K
authors.lastname: Kashani
authors.forename: Matthew
authors.initials: M
authors.lastname: Lissauer
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Walker
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000652:urine*; D000368:Aged; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D012372:ROC Curve; 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
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