Urinary ATP May Be a Dynamic Biomarker of Detrusor Overactivity in Women with Overactive Bladder Syndrome

Abstract

BackgroundNowadays, 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.MethodsPatients 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.ResultsThe 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.ConclusionA 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.

A self-referencing biosensor for real-time monitoring of physiological ATP transport in plant systems

“…According to Gorman et al (2007), human plasma ATP concentrations range from 1 mM in healthy individuals to as low as 28 nM. Silva-Ramos et al (2013) recorded levels of urinary ATP in the range of 2-6 nM for healthy patients and 7-11 nM for patients with overactive bladder syndrome. Jin et al (2004) found ATP concentrations ranging from 2.5 to 32 nM in oral Candida albicans biofilms.…”

Receptors, channels, and signalling in the urothelial sensory system in the bladder

“…Increased levels of urinary ATP have been demonstrated in patients with interstitial cystitis 133 , OAB 134 , and other functional disorders of the urinary bladder 95 . Primary bladder urothelial cells taken from these patients also exhibit increased ATP release in response to mechanical stretch 133 , hypotonic stress 135 , or electrical field stimulation 136 .…”

Purinergic signalling in the urinary tract in health and disease

“…In recent papers it was reported that women with OAB have high urinary levels of ATP compared to controls and the nucleotide levels increase with water intake and it was suggested therefore that higher urinary ATP may be a useful prognostic marker for detrusor overactivity [142,615]. It was suggested that the increased concentrations of ATP in the urine is probably due to enhanced ATP release from proliferating urothelium and that decreased ATP metabolism may also contribute to the high urine levels of ATP [615].…”

“…It was suggested that the increased concentrations of ATP in the urine is probably due to enhanced ATP release from proliferating urothelium and that decreased ATP metabolism may also contribute to the high urine levels of ATP [615]. The ATP concentration in urine was inversely related to the volume at the first desire to void in women patients with OAB [142].…”