Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome

PLoS One. 2013 May 31;8(5):e64696. doi: 10.1371/journal.pone.0064696. Print 2013.

Abstract

Background: Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls.

Methods: Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA.

Results: The urinary content of ATP, but not of NGF, normalized to patients' urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary.

Conclusion: A high area under the receiver operator characteristics (ROC) curve (0.741; 95% CI 0.62-0.86; P<0.001) is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / urine*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Case-Control Studies
  • Creatinine / urine
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Middle Aged
  • Nerve Growth Factor / urine
  • ROC Curve
  • Urinary Bladder, Overactive / diagnosis
  • Urinary Bladder, Overactive / physiopathology
  • Urinary Bladder, Overactive / urine*
  • Urination / physiology
  • Urodynamics*

Substances

  • Biomarkers
  • Adenosine Triphosphate
  • Nerve Growth Factor
  • Creatinine

Grants and funding

The research was partially supported by Fundação para a Ciência e a Tecnologia (FCT projects PTDC/SAU-OSM/104369/2008 and Pest/OE/UI0215/2011), Associação Portuguesa de Urologia and University of Porto/Caixa Geral de Depósitos (Investigação Científica na Pré-Graduação). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.