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• W2169504018 abstract "Rationale: We 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.Objectives: We 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.Methods: We 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 Results: Urinary 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]).Conclusions: Urinary [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)." @default.
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• W2169504018 date "2014-04-15" @default.
• W2169504018 modified "2023-10-17" @default.
• W2169504018 title "Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication" @default.
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• W2169504018 doi "https://doi.org/10.1164/rccm.201401-0077oc" @default.
• W2169504018 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24559465" @default.
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