title: Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.
abstract: Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.
authors.affiliation: Renal Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO. Electronic address: avijayan@dom.wustl.edu.
authors.forename: Anitha
authors.initials: A
authors.lastname: Vijayan
authors.affiliation: Renal Division, University of Colorado Denver and Denver VA Medical Center, Denver, CO.
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
authors.affiliation: Division of Pediatric Nephrology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Askenazi
authors.affiliation: Albany Medical College, Albany, NY.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerda
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
authors.affiliation: Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: Michael
authors.initials: M
authors.lastname: Heung
authors.affiliation: Renal Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Humphreys
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Anesthesia, University of California, San Francisco, San Francisco, CA.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Girish
authors.initials: G
authors.lastname: Mour
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Nolin
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL; Department of Anesthesiology, University of Florida, Gainesville, FL; Department of Surgery, University of Florida, Gainesville, FL.
authors.forename: Azra
authors.initials: A
authors.lastname: Bihorac
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002986:Clinical Trials as Topic; D003663:Decision Trees; D042241:Early Diagnosis; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D018570:Risk Assessment / Q000379:methods*; 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
keywords: Acute kidney injury (AKI); NephroCheck; [TIMP-2] × [IGFBP7]; biomarker; critically ill; decreased kidney function; diagnosis; early detection; insulin-like growth factor binding protein 7; renal dysfunction; risk assessment; tissue inhibitor of metalloproteinase 2