title: Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study.
abstract: BACKGROUND
  Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers whose performance in pediatric ICU patients is largely unknown. In this study, we aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties in relation to identifying children at risk for AKI development.
  
  
  METHODS
  From June 2010 until January 2014, we conducted a prospective observational cohort study of term-born children ages 1 day to 1 year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12 hours up to 72 hours post-admission. Blood samples were assayed for SCr, and urine samples were assayed for uNGAL and KIM-1. The RIFLE (risk, injury, failure, loss, end-stage renal disease) classification as 150%, 200% or 300% of median SCr reference values was used to define AKI.
  
  
  RESULTS
  A total of 100 children were included (80 survived). Their median age at admission was 27.7 days (interquartile range (IQR), 1.5 to 85.5). The median duration of mechanical ventilation was 5.8 days (IQR, 3.1 to 11.4). Thirty-five patients had evidence of AKI within the first 48 hours post-admission, of whom 24 (69%) already had AKI when they entered the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12 hours and between 12 to 24 hours post-admission, respectively. The maximal area under the receiver operating characteristic curve (AUC) for uNGAL was 0.815 (95% confidence interval (CI), 0.685 to 0.945, P < 0.001) at 0 to 6 hours post-admission. The discriminative ability of KIM-1 was moderate, with a largest AUC of 0.737 (95% CI, 0.628 to 0.847; P < 0.001) at 12 to 24 hours post-admission. At the optimal cutoff point (126 ng/ml), uNGAL concentration predicted AKI development correctly in 16 (84%) of 19 children, up to 24 hours before a rise in SCr became apparent.
  
  
  CONCLUSIONS
  Levels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12 hours and 12 to 24 hours post-admission, respectively. uNGAL seems to be a reliable marker for identifying children who will develop AKI 24 hours later.
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. a.zwiers@erasmusmc.nl.|Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. a.zwiers@erasmusmc.nl.
authors.forename: Alexandra J M
authors.initials: AJ
authors.lastname: Zwiers
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. s.dewildt@erasmusmc.nl.|Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. s.dewildt@erasmusmc.nl.
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.affiliation: Department of Biostatistics, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. j.vanrosmalen@erasmusmc.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: van Rosmalen
authors.affiliation: Department of Clinical Chemistry, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. y.derijke@erasmusmc.nl.|Department of Internal Medicine, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. y.derijke@erasmusmc.nl.
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. e.a.b.buijs@erasmusmc.nl.|Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. e.a.b.buijs@erasmusmc.nl.
authors.forename: Erik A B
authors.initials: EA
authors.lastname: Buijs
authors.affiliation: Intensive Care and Department of Pediatric Surgery, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. d.tibboel@erasmusmc.nl.|Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. d.tibboel@erasmusmc.nl.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. k.cransberg@erasmusmc.nl.
authors.forename: Karlien
authors.initials: K
authors.lastname: Cransberg
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000628:therapy / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D016638:Critical Illness / Q000628:therapy; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric / Q000639:trends*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D010343:Patient Admission / Q000639:trends*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus