title: Proximal tubule proteins are significantly elevated in bladder urine of patients with ureteropelvic junction obstruction and may represent novel biomarkers: A pilot study.
abstract: OBJECTIVE
  Ureteropelvic junction obstruction (UPJO) is the major cause of hydronephrosis in children and may lead to renal injury and early renal dysfunction. However, diagnosis of the degree of obstruction and severity of renal injury relies on invasive and often inconclusive renal scans. Biomarkers from voided urine that detect early renal injury are highly desirable because of their noninvasive collection and their potential to assist in earlier and more reliable diagnosis of the severity of obstruction. Early in response to UPJO, increased intrarenal pressure directly impacts the proximal tubule brush border. We hypothesize that single-pass, apically expressed proximal tubule brush border proteins will be shed into the urine early and rapidly and will be reliable noninvasive urinary biomarkers, providing the tools for a more reliable stratification of UPJO patients.
  
  
  METHODS
  We performed a prospective cohort study at Connecticut Children's Medical Center. Bladder urine samples from 12 UPJO patients were obtained prior to surgical intervention. Control urine samples were collected from healthy pediatric patients presenting with primary nocturnal enuresis. We determined levels of NGAL, KIM-1 (previously identified biomarkers), CD10, CD13, and CD26 (potentially novel biomarkers) by ELISA in control and experimental urine samples. Urinary creatinine levels were used to normalize the urinary protein levels measured by ELISA.
  
  
  RESULTS
  Each of the proximal tubule proteins outperformed the previously published biomarkers. No differences in urinary NGAL and KIM-1 levels were observed between control and obstructed patients (p = 0.932 and p = 0.799, respectively). However, levels of CD10, CD13, and CD26 were significantly higher in the voided urine of obstructed individuals when compared with controls (p = 0.002, p = 0.024, and p = 0.007, respectively) (Figure).
  
  
  CONCLUSIONS
  Targeted identification of reliable, noninvasive biomarkers of renal injury is critical to aid in diagnosing patients at risk, guiding therapeutic decisions and monitoring treatment efficacy. Proximal tubule brush border proteins are reliably detected in the urine of obstructed patients and may be more effective at predicting UPJO.
authors.affiliation: Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Gerber
authors.affiliation: Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT, USA; Division of Urology, Department of Surgery, Connecticut Children's Medical Center, Hartford, CT, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Harel
authors.affiliation: Center for Quantitative Medicine and Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Lynch
authors.affiliation: Division of Urology, Department of Surgery, Connecticut Children's Medical Center, Hartford, CT, USA.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Herbst
authors.affiliation: Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT, USA; Division of Urology, Department of Surgery, Connecticut Children's Medical Center, Hartford, CT, USA. Electronic address: fferrer@connecticutchildrens.org.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Ferrer
authors.affiliation: Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT, USA; Division of Urology, Department of Surgery, Connecticut Children's Medical Center, Hartford, CT, USA. Electronic address: lshapiro@uchc.edu.
authors.forename: Linda H
authors.initials: LH
authors.lastname: Shapiro
mesh_terms: D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D006869:Hydronephrosis / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D007223:Infant; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D014517:Ureteral Obstruction / Q000150:complications / Q000175:diagnosis / Q000652:urine*; D001743:Urinary Bladder / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2
keywords: Biological markers; Proximal tubules; Ureteral obstruction; Urinary bladder