Hypothesis / aims of study
Purines are important regulators of bladder function and furthermore are involved in the pathophysiology of several bladder dysfunctions. Several studies have shown that the urothelium releases ATP in response to mechanical stimuli, like stretch and local pressure (1). ATP release to the serosal side may activate P2X# receptors in suburothelial nerves and convey sensors information to the central nervous system. But there is significant evidence, mostly coming from Ussing chamber experiments, demonstrating that most of ATP is released to the luminal side of the urothelium (2), and therefore can be measured in the urine. Urinary ATP concentrations have been shown to be elevated in patients with LUTS due to benign prostatic obstruction and to be directly co-related to voided volume, suggesting that urothelium stretch impacts on urinary ATP concentration(3). We investigated if bladder pressure during voiding also influences urinary ATP concentrations.
Study design, materials and methods
Male patients which had a scheduled urodynamic study for the investigation of LUTS were recruited. Patients with urinary tract infection, pelvic radiotherapy, macroscopic hematuria, renal impairment (Chronic Kidney Disease Stage > 2), known neurological disease, with indwelling urinary catheter or undergoing intermittent self-catheterization were excluded. Patients were asked to perform a uroflowmetry at normal desire to void, afterwards the bladder was catheterized with a 7Fr double lumen catheter and residual urine volume was measured. Subsequently a standard filling cistometry and a pressure-flow study were performed complying with good urodynamic practice guidelines. Patients with voided volumes < 50cc or with incomplete urodynamics were also excluded from analysis. A urine sample was collected from the uroflow at beginning of the study and snap frozen in liquid nitrogen and preserved at −80°C until ATP determination. ATP measurement was done using a luciferine-liciferase assay. Normality of data distribution was assessed by Kolmogorov-Smirnov Test and significant correlation between variables was evaluated using Pearson´s R test
Results
A total of 50 patients were included in the analysis. Mean age was 59,8 [27-80] years and mean urinary ATP was 2,95 [0,45-12,53] nM. Urinary ATP concentrations significantly(p<0,001) and directly correlate to Pdet@Qmax (r=0,689), bladder outlet obstruction index (r=0,640) and bladder contractility index (r=0,561) . Correlation between urinary ATP and Pdet@Qmax was independent of voided volume (p<0,001). Mean urinary ATP was similar between patients with and without detrusor 3,05 nM [0,6 - 6,8] and 2,87 nM [0,5-6,4) respectively. In this population patients with detrusor overactivity did´t have higher Pdet@qmax or higher bladder outlet obstruction index.
Interpretation of results
Voiding dynamics affects urinary ATP concentrations. Higher detrusor pressures during voiding may cause higher ATP release from the urothelium resulting in higher urinary ATP concentrations. This effect is independent of the voided volume and therefore of the stretch induced ATP release. Thus, in men detrusor pressure more than bladder distention impacts on urinary ATP concentrations.
The presence of detrusor overactivity didn´t significantly affect urinary ATP concentrations in this population contrary to what has been shown in women. This may be indicate that voiding dynamics impacts more on urinary ATP concentrations than filling phase events.
The significant correlation between urinary ATP and detrusor pressure during voiding may an important way to non-invasively assess detrusor competence during voiding.