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

https://doi.org/10.1016/j.jacc.2011.08.017Get rights and content
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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 (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 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.

Key Words

acute kidney injury
biomarkers
cardiopulmonary bypass
ischemia

Abbreviations and Acronyms

AKI
acute kidney injury
AUC
area under the curve
CPB
cardiopulmonary bypass
eCCl
estimated creatinine clearance
ELISA
enzyme-linked immunosorbent assay
IDI
integrated discrimination improvement
IL
interleukin
KIM
kidney injury molecule
L-FABP
liver fatty acid-binding protein
LOS
length of stay
NGAL
neutrophil gelatinase-associated lipocalin
NRI
net reclassification improvement
pRIFLE
pediatric modified Risk, Injury, Failure, Loss, and End-Stage Kidney Disease
RACHS-1
Risk Adjustment for Congenital Heart Surgery Score version 1
ROC
receiver-operating characteristic
SCr
serum creatinine

Cited by (0)

This study was supported by National Institutes of Health grants no. R01-HL08676, R01-HL085757, and R01-DK069749. Dr. Devarajan is a co-inventor on patents related to neutrophil gelatinase-associated lipocalin; is a consultant to Abbott Diagnostics and Biosite, Inc.; and is on the Speaker's Bureau of Abbott Diagnostics and Alere, Inc.

All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.