title: Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass.
abstract: OBJECTIVE
  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.
authors.affiliation: The Heart Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Krawczeski
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Woo
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Nuntawan
authors.initials: N
authors.lastname: Piyaphanee
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D000367:Age Factors; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D007902:Length of Stay / Q000706:statistics & numerical data; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine
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