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

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 (R) Test (Astute Medical). The test is comprised of fluorescence immunoassays for IGFBP7 and TIMP-2 and is used with the ASTUTE1408 (R) 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]center dot[TIMP-2]) expressed in (ng/ml)(2)/1000 which is called the AKIRISK (TM) Score. Results: The reference intervals (inner 95%) for [IGFBP7]center dot[TIMP-2] in all subjects (N = 750), apparently healthy subjects, and subjects with stable chronic morbidities were 0.04-222, 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]center dot[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI. (C) 2015 The Authors. Published by Elsevier B.V.