A pilot study to investigate the associations of urinary concentrations of NO, ATP and derivatives with overactive bladder symptom severity.

Abstract

What is the central question of this study? Are the urinary concentrations of NO and ATP, and their metabolites, associated with the severity of symptoms of overactive bladder? What is the main finding and its importance? The urinary ratios of [ATP/NO], [ADP/NO] and a combination of these, [ATP/Cr*ADP/Cr]/[NO/Cr], were correlated with overall OAB symptom severity, with the latter combination also being correlated with the severity of urinary frequency and urgency symptoms individually. Together, these data reveal changes in urothelial signalling that accompany the transition from physiology to pathology. Overactive bladder (OAB) is a highly prevalent symptom complex characterized by symptoms of urinary urgency and increased frequency and waking to void (nocturia), with or without urge incontinence and in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known, and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. Nitric oxide, ATP and their metabolites have previously been shown to underlie the perception of bladder fullness, with their release modifying the pathological perception of urgency. Therefore, in this study we assessed the concentrations of NO, ATP and associated metabolites in the urine of 113 consenting participants recruited from the general population. Recruited participants completed a questionnaire to measure the severity of OAB-associated urinary symptoms and provided a mid-stream urine sample. After identification of infection and haematuria using microbiology and microscopy, 95 samples were subjected to assays to measure NO, NO2- , NO3- , ATP, ADP and creatinine (Cr). There was no correlation between [NO/Cr], [NO2- /Cr] or [NO3- /Cr] and overall OAB symptom severity. In contrast, [ATP/NO], [ADP/NO] and a combination of these, [ATP/Cr*ADP/Cr]/[NO/Cr], were correlated with OAB symptom severity, and [ATP/Cr*ADP/Cr]/[NO/Cr] was also correlated with the severity of urinary frequency and urgency. This study adds to a growing literature that demonstrates the potential of urinary biomarkers and provides a foundation for a larger, longitudinal study.