Key result
Post-CPB urine NGAL improves pediatric AKI prediction, boosting AUC to 0.85 over clinical models alone.
Why the study?
Serum creatinine is a delayed marker for AKI after cardiopulmonary bypass, and rapidly detectable urinary biomarkers could allow earlier intervention and improved outcomes.
Do urinary biomarkers (NGAL, IL-18, L-FABP, KIM-1) improve the early prediction of acute kidney injury in pediatric patients after cardiopulmonary bypass?
Observational (n=220)
Do urinary biomarkers (NGAL, IL-18, L-FABP, KIM-1) improve the early prediction of acute kidney injury in pediatric patients after cardiopulmonary bypass?
Effect estimate: AUC 0.85
p-value: p=<0.0001
Urinary biomarkers, particularly NGAL at 2 hours post-CPB, significantly improve the early prediction of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass.
May facilitate earlier AKI detection after pediatric heart surgery; hypothesis-generating pending interventional trials.
Objectives We investigated the temporal pattern and predictive value (alone and in combination) of four urinary biomarkers [neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver fatty-acid binding protein (L-FABP) and kidney injury molecule-1 (KIM-1)] for cardiac surgery-associated acute kidney injury (AKI). Background Serum creatinine (SCr) 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 SCr from baseline within 48h 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 AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2h after CPB initiation. IL-18 and L-FABP increased at 6h and KIM-1 increased at 12h. Biomarker elevations correlated with AKI severity and clinical outcomes, and improved AKI prediction above a clinical model. At 2h, addition of NGAL increased the AUC from 0.74 to 0.85 (p<0.0001). At 6h, 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 NRI and IDI. Biomarker combinations further improved AKI prediction. Conclusion Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and correlate 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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Krawczeski et al. (2011) conducted an observational in cardiac surgery-associated acute kidney injury (n=220). Urinary biomarkers (NGAL, IL-18, L-FABP, KIM-1) vs. Clinical model was evaluated on Acute kidney injury (≥50% increase in SCr from baseline within 48h after CPB) (AUC 0.85, p=<0.0001). Addition of urine NGAL at 2 hours after pediatric cardiopulmonary bypass significantly improved acute kidney injury prediction over a clinical model (AUC increased from 0.74 to 0.85, p<0.0001).
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