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

The Heart Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 11/2011; 58(22):2301-9. DOI: 10.1016/j.jacc.2011.08.017
Source: PubMed


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).
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.
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.
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.
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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    • "It is therefore expected to increase in dogs with heatstroke , which invariably have severe kidney tubular injury (Bruchim et al., 2009). In humans, NGAL is induced as early as 2 h following kidney injury, and it is also extremely sensitive for detecting AKI in dogs at risk, early in the course of disease (Mishra et al., 2003; Krawczeski et al., 2011). Confirming the results of previous canine studies, UNGAL was increased in all dogs with heatstroke, further indicating that dogs with heatstroke have already sustained kidney injury at presentation, even though sCr was within reference intervals in some. "
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    • "Although plasma NGAL was increased in AKI patients in this study, neither increased levels of plasma or urinary NGAL were reliable predictors of AKI post cardiac surgery. Several other studies reporting increased NGAL as a sensitive and specific predictor of AKI after cardiac surgery have used urinary NGAL and described paediatric populations (Bennett et al., 2008; Krawczeski et al., 2011; Mishra et al., 2005). In the adult cardiac surgery population, several authors, in line with our findings, have reported NGAL as a postoperative marker with variable performance in the prediction of AKI (Liangos et al., 2009; Peco-Antic et al., 2013; Sargentini et al., 2012; Wagener et al., 2008). "
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    ABSTRACT: Abstract Context: Cardiac surgery. Objective: To compare plasma and urinary neutrophil gelatinase-associated lipocalin (P-/U-NGAL) in on-pump (n = 43) versus off-pump (n = 40) surgery. Materials and methods: We obtained perioperative P-/U-NGAL and outcome data. Results: P-/U-NGAL increased after surgery. P-NGAL was higher post-surgery in on pump patients (139 versus 67 µg L(-1); p < 0.001), but not at 24 h. There were no differences in U-NGAL. Correlation between P-/U-NGAL and plasma creatinine was weak. Discussion: P-NGAL acts like a neutrophil activation biomarker and U-NGAL like a tubular injury marker. Conclusion: On-pump patients had greater neutrophil activation. On- versus off-pump surgery had similar impact on tubular cells.
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    • "Finally, our AKI definition has significant shortcomings. It did not include urine output as intraoperative ultrafiltration and early postoperative diuretics could have influenced it [21]. "
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