title: Reference intervals of urinary acute kidney injury (AKI) markers [IGFBP7]∙[TIMP2] in apparently healthy subjects and chronic comorbid subjects without AKI.
abstract: BACKGROUND
  Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) have demonstrated significantly improved diagnostic performance in assessing risk for acute kidney injury (AKI) compared with existing biomarkers. We present the findings of a multi-site trial to determine the reference intervals for these biomarkers in apparently healthy adults and those with stable chronic morbid conditions without AKI.
  
  
  METHODS
  A urine specimen was collected from apparently healthy subjects (N=378) and subjects with at least one stable chronic morbidity (N=372). Specimens were kept frozen until analysis with the NephroCheck® Test (Astute Medical). The test is comprised of fluorescence immunoassays for IGFBP7 and TIMP-2 and is used with the Astute140® Meter which quantifies the concentration of each biomarker. The meter multiplies the concentrations of IGFBP7 and TIMP-2 and displays the result as a numerical value ([IGFBP7]∙[TIMP-2]) expressed in (ng/ml)(2)/1000 which is called the AKIRisk™ Score.
  
  
  RESULTS
  The reference intervals (inner 95%) for [IGFBP7]∙[TIMP-2] in all subjects (N=750), apparently healthy subjects, and subjects with stable chronic morbidities were 0.04-2.22, 0.04-2.25, and 0.05-2.20 (ng/ml)(2)/1000 respectively. There was no statistical difference between reference intervals for apparently healthy and chronic stable morbid cohorts (p=0.42).
  
  
  CONCLUSIONS
  Our investigation showed that urine [IGFBP7]∙[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI.
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California-San Diego Health Systems, San Diego, CA, United States.
authors.forename: Nandkishor S
authors.initials: NS
authors.lastname: Chindarkar
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, DC, United States.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Department of Pathology and ARUP Laboratories, University of Utah School of Medicine, Salt Lake City, UT, United States.
authors.forename: Joely A
authors.initials: JA
authors.lastname: Straseski
authors.affiliation: Department of Pathology, University of Louisville, Louisville, KY, United States.
authors.forename: Saeed A
authors.initials: SA
authors.lastname: Jortani
authors.affiliation: John T. Mather Memorial Hospital, Port Jefferson, NY, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Uettwiller-Geiger
authors.affiliation: Phoenix Medical Group, Peoria, AZ, United States.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Orr
authors.affiliation: Center for Critical Care Nephrology Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Pathology, Center for Advanced Laboratory Medicine, University of California-San Diego Health Systems, San Diego, CA, United States. Electronic address: rfitzgerald@ucsd.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fitzgerald
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002908:Chronic Disease; D005260:Female; D005453:Fluorescence; D064368:Healthy Volunteers; D006801:Humans; D007118:Immunoassay; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; 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; Cell-cycle arrest; Insulin-like growth factor-binding protein 7 (IGFBP7); Nephrocheck; Reference interval; Tissue inhibitor of metalloproteinases-2 (TIMP-2)