title: Pediatric reference ranges for acute kidney injury biomarkers.
abstract: BACKGROUND
  Novel urinary biomarkers are useful for the prediction of acute kidney injury (AKI). Most promising are the urine markers NGAL, IL-18, KIM-1, and LFABP. Each of these has shown considerable promise diagnosing AKI earlier than serum creatinine (Scr) using disease controls. We set out to determine reference levels of these markers in a healthy pediatric population.
  
  
  METHODS
  Urine was collected from 368 healthy children and assayed for NGAL, IL-18, KIM-1, and LFABP using commercially available kits or assay materials. Analysis of biomarkers by linear regression and according to age groups (3-<5 years; 5-<10; 10-<15; 15-<18) was performed to determine if biomarker levels differed with age and gender.
  
  
  RESULTS
  Median values were: NGAL (6.6 ng/ml; IQR 2.8-17), IL-18 (21.6 pg/ml; IQR 13.6-32.9), KIM-1 (410 pg/ml; IQR 226-703), LFABP (3.4 ng/ml; IQR 1.6-6.0). Significant gender differences were found with NGAL and IL-18 and significant age differences were found with all markers. 95th percentile values for each marker varied with age and gender greater than median values.
  
  
  CONCLUSIONS
  This is the largest pediatric reference range study for the urinary measurement of NGAL, IL-18, KIM-1, and LFABP and highlights age and gender differences in these markers. This information is essential for rational interpretation of studies and clinical trials utilizing these emerging AKI biomarkers.
authors.affiliation: Biomarker Laboratory, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, ML 7022, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA, michael.bennett@cchmc.org.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.forename: Edward
authors.initials: E
authors.lastname: Nehus
authors.forename: Christopher
authors.initials: C
authors.lastname: Haffner
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
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; D000293:Adolescent; D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008562:Membrane Glycoproteins / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D012016:Reference Values
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