4.7 Article

Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass

Journal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 58, Issue 22, Pages 2301-2309

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2011.08.017

Keywords

acute kidney injury; biomarkers; cardiopulmonary bypass; ischemia

Funding

  1. National Institutes of Health [R01-HL08676, R01-HL085757, R01-DK069749]

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Objectives We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI). Background Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. Methods Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a >= 50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement. Results AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction. Conclusions Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI. (J Am Coll Cardiol 2011;58:2301-9) (C) 2011 by the American College of Cardiology Foundation

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