TY - JOUR
T1 - Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication
AU - Bihorac, Azra
AU - Chawla, Lakhmir S.
AU - Shaw, Andrew D.
AU - Al-Khafaji, Ali
AU - Davison, Danielle L.
AU - DeMuth, George E.
AU - Fitzgerald, Robert
AU - Gong, Michelle Ng
AU - Graham, Derrel D.
AU - Gunnerson, Kyle
AU - Heung, Michael
AU - Jortani, Saeed
AU - Kleerup, Eric
AU - Koyner, Jay L.
AU - Krell, Kenneth
AU - LeTourneau, Jennifer
AU - Lissauer, Matthew
AU - Miner, James
AU - Nguyen, H. Bryant
AU - Ortega, Luis M.
AU - Self, Wesley H.
AU - Sellman, Richard
AU - Shi, Jing
AU - Straseski, Joely
AU - Szalados, James E.
AU - Wilber, Scott T.
AU - Walker, Michael G.
AU - Wilson, Jason
AU - Wunderink, Richard
AU - Zimmerman, Janice
AU - Kellum, John A.
PY - 2014/4/15
Y1 - 2014/4/15
N2 - 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]d [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]d[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 endpointwas reached in 17%of patients. For a single urinary [TIMP-2]d [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]d[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]d[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]d[IGFBP7]). Conclusions: Urinary [TIMP-2]d[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).
AB - 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]d [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]d[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 endpointwas reached in 17%of patients. For a single urinary [TIMP-2]d [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]d[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]d[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]d[IGFBP7]). Conclusions: Urinary [TIMP-2]d[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).
KW - Acute kidney injury
KW - Biomarkers
KW - Cell-cycle arrest
KW - Insulin-like growth factor binding protein 7
KW - Tissue inhibitor of metalloproteinases-2
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U2 - 10.1164/rccm.201401-0077OC
DO - 10.1164/rccm.201401-0077OC
M3 - Article
C2 - 24559465
AN - SCOPUS:84899023880
SN - 1073-449X
VL - 189
SP - 932
EP - 939
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 8
ER -