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. 2011 Nov 22;58(22):2301-9.
doi: 10.1016/j.jacc.2011.08.017.

Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass

Catherine D Krawczeski  1 , Stuart L Goldstein, Jessica G Woo, Yu Wang, Nuntawan Piyaphanee, Qing Ma, Michael Bennett, Prasad Devarajan
Affiliations

Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass

Catherine D Krawczeski et al. J Am Coll Cardiol. .

Abstract

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.

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Figures

Figure 1
Figure 1. Urine biomarker concentrations by AKI status
Median and interquartile range (IQR) are presented. Statistically significant differences (p<0.0001) in medians between AKI and non-AKI patients are denoted by *. A: urine NGAL; B: urine IL-18; C: urine L-FABP; D: urine KIM-1.
Figure 2
Figure 2. Urine biomarker concentrations by pRIFLE categories
Median and interquartile range (IQR) are presented. Medians were compared between pRIFLE categories. Statistically significant differences (p<0.05) in medians are denoted by letters: a (F vs. no AKI), b (I vs. no AKI), c (R vs. no AKI), d (F vs. R), e (F vs. I), f (I vs. R). A: urine NGAL; B: urine IL-18; C: urine L-FABP; D: urine KIM-1.
Figure 3
Figure 3. Receiver operating characteristic (ROC) curves for prediction of AKI using urine biomarkers at time intervals following cardiopulmonary bypass (CPB)
A: T=2h; B: T=6h; C: T=12h; D: T=24h.
See this image and copyright information in PMC

Comment in

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