Reference intervals of urinary acute kidney injury (AKI) markers [IGFBP7]∙[TIMP2] in apparently healthy subjects and chronic comorbid subjects without AKI

Clin Chim Acta. 2016 Jan 15;452:32-7. doi: 10.1016/j.cca.2015.10.029. Epub 2015 Nov 10.


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.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / urine*
  • Adult
  • Aged
  • Biomarkers / urine
  • Chronic Disease
  • Female
  • Fluorescence
  • Healthy Volunteers
  • Humans
  • Immunoassay
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Male
  • Middle Aged
  • Reference Values
  • Tissue Inhibitor of Metalloproteinase-2 / urine*


  • Biomarkers
  • Insulin-Like Growth Factor Binding Proteins
  • TIMP2 protein, human
  • insulin-like growth factor binding protein-related protein 1
  • Tissue Inhibitor of Metalloproteinase-2