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Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication

American journal of respiratory and critical care medicine, 2014-04, Vol.189 (8), p.932-939 [Peer Reviewed Journal]

2015 INIST-CNRS ;Copyright American Thoracic Society Apr 15, 2014 ;ISSN: 1073-449X ;EISSN: 1535-4970 ;DOI: 10.1164/rccm.201401-0077oc ;PMID: 24559465

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Title:
Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication
Author: BIHORAC, Azra ; CHAWLA, Lakhmir S ; HEUNG, Michael ; JORTANI, Saeed ; KLEERUP, Eric ; KOYNER, Jay L ; KRELL, Kenneth ; LETOURNEAU, Jennifer ; LISSAUER, Matthew ; MINER, James ; NGUYEN, H. Bryant ; ORTEGA, Luis M ; SHAW, Andrew D ; SELF, Wesley H ; SELLMAN, Richard ; JING SHI ; STRASESKI, Joely ; SZALADOS, James E ; WILBER, Scott T ; WALKER, Michael G ; WILSON, Jason ; WUNDERINK, Richard ; ZIMMERMAN, Janice ; AL-KHAFAJI, Ali ; KELLUM, John A ; DAVISON, Danielle L ; DEMUTH, George E ; FITZGERALD, Robert ; NG GONG, Michelle ; GRAHAM, Derrel D ; GUNNERSON, Kyle
Subjects: Acute Kidney Injury - diagnosis ; Acute Kidney Injury - urine ; Aged ; Aged, 80 and over ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Biological and medical sciences ; Biomarkers - urine ; Cell Death ; Cohort Studies ; Critical Illness ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins - urine ; Intensive care medicine ; Kidneys ; Male ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Pneumology ; Predictive Value of Tests ; Prospective Studies ; Protease Inhibitors - urine ; Sensitivity and Specificity ; Severity of Illness Index ; Time Factors ; Tissue Inhibitor of Metalloproteinase-2 - urine ; United States ; Urinary system involvement in other diseases. Miscellaneous
Is Part Of: American journal of respiratory and critical care medicine, 2014-04, Vol.189 (8), p.932-939
Description: 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. 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. 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. 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]). 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).
Publisher: New York, NY: American Thoracic Society
Language: English
Identifier: ISSN: 1073-449X
EISSN: 1535-4970
DOI: 10.1164/rccm.201401-0077oc
PMID: 24559465
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
Alma/SFX Local Collection
ProQuest Central

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Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication

2015 INIST-CNRS ;Copyright American Thoracic Society Apr 15, 2014 ;ISSN: 1073-449X ;EISSN: 1535-4970 ;DOI: 10.1164/rccm.201401-0077oc ;PMID: 24559465

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