Abstract
To determine whether the amount of ATP, prostaglandin E2 (PGE2 ), and acetylcholine (ACh) in voided urine are influenced enough by that released within the lower urinary tract (LUT) for them to be useful biomarkers of bladder function. Participants without LUT symptoms collected total urine voids at 15, 30, 60, and 120 min (20 males/23 females) and 240 min (18 males/26 females) following the previous void. Aliquots of urine were immediately frozen at -20°C and later used to measure ATP (luciferin-luciferase), PGE2 (enzyme-linked immunosorbent assay), ACh (mass spectrometry), creatinine (colorimetric), and lactose dehydrogenase (colorimetric). The amount of ATP in voided urine correlated strongly with the rate of urine production, suggesting that the majority, if not all, the ATP in voided urine has an LUT, and likely bladder, origin. In contrast, there appeared to be no significant net LUTs release of creatinine or ACh into the urine. PGE2 was intermediate with an LUT component that increased with urine production rate and contributed about 25% of the total at 1 ml/min in women but a smaller fraction in men. Whereas the majority of the ATP measured within the voided urine originates in the LUT, ACh reflects that extracted from the plasma in the kidneys and PGE2 is a mixture of both sources. ATP has the most potential as a biomarker of benign bladder disorders. Expressing urinary ATP concentration relative to creatinine concentration is questioned in light of these results.
Highlights
| INTRODUCTIONMeasuring the concentration of transmitters within the urine as possible biomarkers of benign bladder disorders is increasingly relevant to investigate pathological origins.[1,2] ATP, prostaglandin E2 (PGE2), and acetylcholine (ACh) are all potential candidates[3,4] but to be useful as a urinary biomarker a significant fraction of that measurable in the urine must have a lower urinary tract (LUT) origin
The concentrations of creatinine, ATP, ACh, and prostaglandin E2 (PGE2) were measured for each urine sample and plotted as a function of the time to produce each microliter of urine, the inverse of urine production rate (Figure 1)
No significant positive correlation was observed between ATP concentration and time to produce each microliter of urine from either women or men, indicating that ATP concentration in the urine varies in a ATP concentration was significantly higher in women than men [median: women (n = 117), 3.6 nmol/l (2.5–5.9); men (n = 91), 1.3 nmol/l (1.0–2.1); p < .001], which was not the case for creatinine, ACh, or PGE2
Summary
Measuring the concentration of transmitters within the urine as possible biomarkers of benign bladder disorders is increasingly relevant to investigate pathological origins.[1,2] ATP, prostaglandin E2 (PGE2), and acetylcholine (ACh) are all potential candidates[3,4] but to be useful as a urinary biomarker a significant fraction of that measurable in the urine must have a lower urinary tract (LUT) origin. The purpose of this study was to investigate the extent to which secretion or reabsorption of potential biomarkers across the LUT contributes to the amount of ATP, ACh, and PGE2 within the voided urine and how this is affected by the rate of urine production. This has implications for how best to compare the levels in urine samples from different human subjects and between samples from the same individual and whether expressing their concentration relative to that of creatinine is useful
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