title: Evaluation of novel urinary tract infection biomarkers in children.
abstract: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children.
  
  
  
  We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1-3, and test combinations were compared.
  
  
  
  For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82-0.93), respectively. Compared to LE ≥ trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone.
  
  
  
  Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children.
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Joshua R
authors.identifier: 0000-0003-0079-937X
authors.initials: JR
authors.lastname: Watson
authors.affiliation: Innate Immunity Translational Research Center, Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hains
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Cohen
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: John David
authors.initials: JD
authors.lastname: Spencer
authors.affiliation: Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kline
authors.affiliation: Biostatistics Core, Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Schwaderer
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D057286:Electronic Health Records; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010372:Pediatrics; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity; D016482:Urinalysis; D014552:Urinary Tract Infections / Q000652:urine*; D023084:alpha-Defensins / Q000652:urine*
chemical_list: D015415:Biomarkers; C500225:DEFA5 protein, human; D023084:alpha-Defensins