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Nephrol Dial Transplant. 2014 Nov;29(11):2054-61. doi: 10.1093/ndt/gfu292. Epub 2014 Sep 18.

Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers.

Author information

1
Intensive Care Unit, Ghent University Hospital, Ghent University, and Research Foundation-Flanders (FWO), Belgium.
2
Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX The Heart Hospital, Plano, TX.
3
Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
4
Department of Medicine, Division of Intensive Care Medicine, and the Division of Nephrology, Washington, DC, Veterans Affairs Medical Center Department of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
5
Department of Internal Medicine, ICU, Medical University Innsbruck, Innsbruck, Austria.
6
Department of Anesthesia, Vanderbilt University Medical Center, Nashville, TN, USA.
7
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Germany Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany.
8
Clinical Laboratory Trials, JT Mather Memorial Hospital, Port Jefferson, NY, USA.
9
Critical Care Medicine, R Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, MD, USA.
10
Walker Biosciences, Carlsbad, CA, USA.
11
Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.

Abstract

BACKGROUND:

Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers.

METHODS:

We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2-3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the USA.

RESULTS:

One hundred subjects (14%) in Sapphire and 27 (18%) in Opal met the primary end point. The results of the Opal study replicated those of Sapphire. Relative risk (95% CI) in both studies for subjects testing at ≤0.3 versus >0.3-2 were 4.7 (1.5-16) and 4.4 (2.5-8.7), or 12 (4.2-40) and 18 (10-37) for ≤0.3 versus >2. For the 0.3 cutoff, sensitivity was 89% in both studies, and specificity 50 and 53%. For 2.0, sensitivity was 42 and 44%, and specificity 95 and 90%.

CONCLUSIONS:

Urinary [TIMP-2]•[IGFBP7] values of 0.3 or greater identify patients at high risk and those >2 at highest risk for AKI and provide new information to support clinical decision-making.

CLINICAL TRIALS REGISTRATION:

Clintrials.gov # NCT01209169 (Sapphire) and NCT01846884 (Opal).

KEYWORDS:

acute kidney injury; acute renal failure; biomarkers; insulin-like growth factor binding protein (IGFBP)7 and tissue inhibitor of metalloproteinases (TIMP)-2; sensitivity and specificity (MeSH)

PMID:
25237065
PMCID:
PMC4209880
DOI:
10.1093/ndt/gfu292
[Indexed for MEDLINE]
Free PMC Article

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