title: Analytical characteristics of a biomarker-based risk assessment test for acute kidney injury (AKI).
abstract: BACKGROUND
  Acute kidney injury (AKI) is associated with increased mortality, morbidity, hospital length of stay, and costs. A quantitative urine test is available to assess the risk of developing AKI by measuring the concentrations of two protein biomarkers, TIMP-2 and IGFBP-7. The NephroCheck Test combines these concentrations into an AKIRisk Score. The purpose of this study is to characterize the analytical performance characteristics of the AKIRisk Score.
  
  
  METHODS
  Linearity and analytical sensitivity were evaluated by following Clinical Laboratory Standards Institute (CLSI) EP06-A and EP17-A, respectively. Precision was evaluated by testing clinical samples and examining the repeatability of test results. Potential interference was evaluated for endogenous and exogenous substances. Sample stability was examined at room temperature and at 2-8°C, as well as the effect of sample centrifugation temperature on test results.
  
  
  RESULTS
  The AKIRisk Score exhibits approximately 10% coefficient of variation (CV) at the recommended cutoff value of 0.3 and the limit of quantitation (LoQ) was 0.002. Only albumin, bilirubin (conjugated), and methylene blue interfered with test results, at concentrations exceeding 1250 mg/L, 72 mg/L, and 0.49 mg/L, respectively. AKIRisk Score results were stable for 6h at room temperature, 24h refrigerated, and not impacted by sample centrifugation temperature.
  
  
  CONCLUSIONS
  Our studies demonstrate that the AKIRisk Score has robust analytical performance, good precision, minimal analytical interference, acceptable sensitivity, and excellent sample stability.
authors.affiliation: John T. Mather Memorial Hospital, Port Jefferson, NY, United States. Electronic address: dgeiger@matherhospital.org.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Uettwiller-Geiger
authors.affiliation: Astute Medical, Inc., San Diego, CA, United States.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vijayendran
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.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fitzgerald
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000652:urine*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D007674:Kidney Diseases / Q000652:urine*; D057230:Limit of Detection; D015203:Reproducibility of Results; D018570:Risk Assessment; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: AKIRisk score; Acute kidney injury (AKI); Insulin-like growth factor binding protein 7 (IGFBP-7); Interference; KDIGO: kidney disease improving global outcomes; Limit-of-detection; Precision; Sample stability; Tissue inhibitor of metalloproteinase 2 (TIMP-2)