A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment

Skorupska

et al. 2020

JCM

The aim of this study was to assess the effectiveness of vaginal native tissue repair (VNTR) on preexisting Lower Urinary Tract Symptoms (LUTS) in women with symptomatic pelvic organ prolapse (POP). Two hundred patients who underwent VNTR for symptomatic POP from January 2018 to February 2019 were followed up for 6 months. All patients underwent VNTR, but in the posterior compartment, the rectovaginal fascia was reconnected to the uterosacral ligaments and additionally sutured to the iliococcygeus fascia and muscle. To assess the severity and change in storage phase LUTS before and after surgery, all participants were asked to complete 3 questionnaires: the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Urogenital Distress Inventory-6 (UDI-6), and Incontinence Impact Questionnaire-7 (IIQ-7). The data were assessed with Statistica package version 12.0, using Kalmogorow-Smirnoff, W Shapiro-Wilk tests. Furthermore, one-way analysis of variance was applied with post-hoc Tukey test. The study results indicate that the majority of patients with advanced POP suffered from various LUTS. Among storage symptoms, the occurrence of urinary incontinence (UI) and urgency decreased significantly after surgery. Moreover, ICIQ-SF, UDI-6, and IIQ-7 results showed statistically significant improvement in the impact of UI on the quality of life (QoL) in the vast majority of patients after surgery. VNTR is an effective way to treat not only anatomical, but also functional problems in such patients.

Section: Discussioncontrasting

confidence: 57%

The Influence of Vaginal Native Tissues Pelvic Floor Reconstructive Surgery in Patients with Symptomatic Pelvic Organ Prolapse on Preexisting Storage Lower Urinary Tract Symptoms (LUTS)

Skorupska

et al. 2020

JCM

Neurourology and Urodynamics

“…To further investigate this observation and the idea that P2Y6 may be a therapeutic target for OAB, P2Y6 expression was quantified and correlated with total OAB symptom severity and the severity of individual symptoms, given a number of symptom combinations (OAB phenotypes) observed clinically. 13 A significant positive correlation was observed between the mucosal expression levels of P2Y6, normalized to β-actin (ie, P2Y6/β-actin), F I G U R E 3 Associations of mucosal P2Y6 receptor expression and urinary adenosine triphosphate (ATP) and adenosine diphosphate (ADP) with total ICIQ-OAB score. Ai, Representative Western blots of P2Y6 (42 KDa, expected band size) and β-actin (47 KDa, expected band size) expressions in human bladder mucosa biopsy samples; +control: human bronchial epithelium lysate; − control: human bronchial epithelium lysate with no P2Y6 primary antibody.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder

Firouzmand

Ajori

Towse

et al. 2020

Aim To characterize purinergic signaling in overactive bladder (OAB). Methods Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid‐stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire – Overactive Bladder) to score urinary symptoms of OAB. Results P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan‐cytokeratin), was more greatly expressed in OAB compared to age‐ and sex‐matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). Conclusions The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Experimental Physiology

“…Overactive bladder is a symptom complex with a profound impact on many aspects of the quality of life (Milsom, Kaplan, Coyne, Sexton, & Kopp, 2012). Our understanding of the pathophysiological mechanisms underlying its development is limited, but an association with many factors has led to the notion of the existence of several OAB phenotypes (Peyronnet et al., 2019), potentially identified by specific urinary biomarkers (Antunes‐Lopes & Cruz, 2019). In the present study, we aimed to investigate the validity of urinary biomarkers in human participants with mild to moderate OAB symptoms, in order to address the utility of these urinary biomarkers in early detection.…”

Section: Discussionmentioning

confidence: 99%

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

Firouzmand

Young

2020

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, NO 2 − , NO 3 − , ATP, ADP and creatinine (Cr). There was no correlation between [NO/Cr], [NO 2 − /Cr] or [NO 3 − /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.