title: Urinary proteome analysis to exclude severe vesicoureteral reflux.
abstract: OBJECTIVE
  High-grade vesicoureteral reflux (VUR, grade IV or V) is a risk factor for renal scarring, impaired renal function, and arterial hypertension. Voiding cystourethrography is the gold standard for detecting the severity of VUR. High-grade VUR is present in the minority of children with urinary tract infection (UTI), thus exposing the majority to invasive diagnostics that have no surgical consequence. We therefore aimed at establishing a noninvasive test to identify children with high-grade VUR.
  
  
  METHODS
  In a case-control study, a specific urinary proteome pattern was established by capillary electrophoresis coupled to mass spectrometry in 18 patients with primary VUR grade IV or V, distinguishing these from 19 patients without VUR after UTI. This proteome pattern was independently validated in a blinded cohort of 17 patients with VUR grade IV or V and 19 patients without VUR.
  
  
  RESULTS
  Sensitivity in detecting VUR grade IV or V in the blinded study was 88%, specificity was 79%. The test's accuracy was independent of age, gender, and grade of VUR in the contralateral kidney. The odds ratio of suffering from VUR grade IV or V when tested positive was 28 (95% confidence interval: 4.5 to 176.0).
  
  
  CONCLUSIONS
  This noninvasive test is ready for prospective validation in large cohorts with the aim of identifying those children with UTI and hydronephrosis in need of further invasive diagnostics, such as voiding cystourethrography, thus sparing most children without pathologic urinary proteome patterns from additional diagnostics.
authors.affiliation: Clinic of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. jens.drube@web.de
authors.forename: Jens
authors.initials: J
authors.lastname: Drube
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Esther
authors.initials: E
authors.lastname: Lau
authors.forename: Claus
authors.initials: C
authors.lastname: Petersen
authors.forename: Martin
authors.initials: M
authors.lastname: Kirschstein
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Kemper
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Benno
authors.initials: B
authors.lastname: Ure
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Lars
authors.initials: L
authors.lastname: Pape
authors.forename: Jochen H H
authors.initials: JH
authors.lastname: Ehrich
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D006869:Hydronephrosis / Q000145:classification / Q000175:diagnosis / Q000652:urine; D007223:Infant; D008297:Male; D013058:Mass Spectrometry; D010455:Peptides / Q000652:urine; D011237:Predictive Value of Tests; D020543:Proteome / Q000032:analysis*; D014463:Ultrasonography; D014552:Urinary Tract Infections / Q000145:classification / Q000175:diagnosis / Q000652:urine; D014718:Vesico-Ureteral Reflux / Q000145:classification / Q000175:diagnosis* / Q000652:urine*
chemical_list: D015415:Biomarkers; D010455:Peptides; D020543:Proteome