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BackgroundInsulin-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.MethodsA 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.ResultsThe 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).ConclusionsOur investigation showed that urine [IGFBP7]∙[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI.

This data in brief describes characteristics of chronic stable comorbid patients who were included in reference range studies of [IGFBP7]·[TIMP-2] "Reference Intervals of Urinary Acute Kidney Injury (AKI) Markers [IGFBP7]·[TIMP2] in Apparently Healthy Subjects and Chronic Comorbid Subjects without AKI" [1]. In order to determine the specificity of [IGFBP7]·[TIMP-2] for identifying patients at risk of developing AKI we studied a cohort with nine broad classification of disease who did not have AKI. Details regarding the population that was targeted for inclusion in the study are also described. Finally, we present data on the inclusion criteria for the healthy subjects used in this investigation to determine the reference range.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).