Adult Bladder Research Articles

Adult Bladder Exstrophy Managed by Complete Primary Repair: A Case Report

Bladder Exstrophic diseases, referred to collectively as Bladder Exstrophy-Epispadiasis complex, are a spectrum of embryological anomalies with a rare prevalence of approximately 3.3 per 1,00,000 live births with a male gender predominance. An 18-year-old man presented to Urology Outpatient Department (OPD) with subumbilical abdominal wall defect, absent anterior bladder wall with epispadiasis and was diagnosed as a case of adult classic bladder exstrophy with Epispadiasis complex. There was no history of any fever, haematuria, dysuria or abdominal pain. His ultrasound abdomen and intravenous pyelography reported normal kidney function. He had a low Body Mass Index (BMI) (17.5 kg/m2 ) with serum creatinine of 0.6 mg/dL. The patient underwent a complete primary repair, including bladder template closure and bladder neck reconstruction using Young-Dees-Leadbetter technique. Epispadias was repaired with the Modified Cantwell-Ransley approach. Abdominal wall defect closure was done with the help of rectus abdominis muscle flap which was later grafted using Split Thickness Skin Graft (STSG). Postoperatively, a small vesicocutaneous fistula developed which healed spontaneously over two weeks period. On follow-up patient was on clean intermittent catheterisation with some incontinence episodes during night-time. Bladder exstrophy in adult patients is rare, as the condition is usually identified in the neonatal period and can be surgically corrected early on. Due to the complexity of the surgery, these cases require thorough multidisciplinary evaluation and careful planning for successful correction.

Risk of dementia associated with anticholinergic drugs for overactive bladder in adults aged ≥55 years: nested case-control study

ObjectiveTo investigate whether different anticholinergic drug treatments for overactive bladder have differential risks for incident dementia, in a large representative population of older adults in England.DesignNested case-control study.SettingGeneral practices in...

Intradetrusor OnabotulinumtoxinA outcomes for overactive bladder in older adults

Introduction:In older adults, pharmacological treatment of overactive bladder (OAB) with anticholinergics and beta-3 agonists could be associated with negative cognitive effects; highlighting the need for alternative treatment modalities. Currently, there is relatively little evidence assessing outcomes of onabotulinomtoxin-A injection as thirdline therapy in this population. This study sought to evaluate the outcomes of intradetrusor BTX-A injection in patients over 70 years of age between August 2014 March 2022. Methods:A retrospective chart review was performed on patients with a clinical diagnosis of OAB and who underwent an initial intradetrusor onabotulinomtoxinA injection at 70 years or older from three US centers. Patient characteristics and self-reported symptoms before and after injection were statistically analyzed. Results:Amongst the 210 patients, 94% reported urinary urgency, 92% reported urgency urinary incontinence, and 89% reported daytime frequency. The most common medications initially prescribed were beta-3 agonist at 66% and anticholinergics at 65%. Following treatment, 80% reported >50% improvement in incontinence, 81% in urgency, 79% in daytime frequency, and 78% in nocturia. Temporary de novo intermittent catheterization was initiated in 8/210 (3.8%) patients, and one (0.5%) required indwelling catheter placement; with 67% returning for repeat injections. Thirty-six (17%) had a symptomatic urinary tract infection at follow-up. Seventy-five percent of patients did not require drug therapy following injection. In a subgroup analysis of octogenarians (n = 50/210), 73% showed improvement in urgency and 68% had less incontinence post-injection. Discussion:OnabotulinomtoxinA was well tolerated in patients older than 70 with improvement in overactive bladder symptoms and reduction in requirement of drug therapy.

Blood cadmium levels and overactive bladder in middle-aged and older adults in the United States: Insights from NHANES 2007–2020 data

Cadmium is a common environmental pollutant associated with various health risks. Its neurotoxic, muscle-damaging, and pro-inflammatory properties may be related to overactive bladder (OAB), though few studies have assessed its impact on urinary function. This study aimed to examine the potential link between cadmium exposure and OAB. Using data from the 2007–2020 National Health and Nutrition Examination Survey (NHANES), we analyzed adults aged 40 and older (n = 15,467) in a cross-sectional design. OAB was defined by the refined Overactive Bladder Symptom Score (OABSS). Weighted multivariate logistic regression examined the associations between blood cadmium levels and OAB and its components. Age and gender stratifications were performed, and restricted cubic splines (RCS) were used to explore non-linear associations between blood cadmium and OAB. Sensitivity analyses and co-exposure analyses with other pollutants were conducted to assess OAB definition stability, subgroup differences, and exposure collinearity. The prevalence of OAB was 26.2%. While blood cadmium showed a small, non-significant positive association with overall OAB, it was inversely associated with nocturia severity (OR = 0.85, 95% CI 0.74–0.98, p < 0.05). Blood cadmium was also linked to more severe urinary incontinence in the 50–59 age group and among non-Hispanic Black adults. A non-linear association between blood cadmium and OAB was observed (p for nonlinearity = 0.016, p < 0.05). In co-exposure analyses, cadmium remained a dominant and independent factor. These findings suggest that cadmium exposure may have a complex association with OAB and may relate differently to its various components. Further research is needed to explore these relationships.

Response to Treatment with Botulinum Neurotoxin A (BoNT-A) in Children and Adolescents with Neurogenic Lower Urinary Tract Dysfunction and Idiopathic Overactive Bladder: A Systematic Review and Meta-Analysis.

Botulinum neurotoxin A (BoNT-A) is a treatment option for neurogenic lower urinary tract dysfunctions (NLUTD) and idiopathic overactive bladder (OAB) in adults. Recently, its use has gained popularity in paediatric urology. Transitional urology deals with adolescents affected by congenital urological issues, who mature into adulthood. The aim of this systematic review was to update the current knowledge on the use of BoNT-A in children and adolescents. A comprehensive search in PubMed, Scopus, and Web of Science databases was performed from articles published up to September 2024. Both prospective and retrospective single-cohort or comparative studies evaluating outcomes of interest were included. These consisted of the amelioration of urinary incontinence (UI), continence rates, improvement of urodynamic parameters (maximum detrusor pressure during voiding, maximum bladder capacity, and bladder compliance), and type and prevalence of adverse/side effects. Qualitative and quantitative data syntheses were provided. Moderators and meta-regression analyses were carried out as well. Forty-one full-text manuscripts were selected of which 26 focused on children with NLUTD, 13 on idiopathic OAB, and two on both conditions. Overall, 1521 patients were included of whom 715 were male, 646 female, and 160 of unknown sex. Mean age varied between 5.6 and 15.6 years. No studies specifically focused on transitional urology, despite patients up to at least 17 years of age being included. Several differences existed in design, type, dose, way of administration, outcomes measured and follow-up time; however, all studies independently showed an improvement of UI and urodynamic parameters with no major side/adverse events. Pooled analysis showed a mean rate of improvement in UI scores/episodes of 75.87% within a period of 3-6 months following BoNT-A treatment. Meta-regression analyses demonstrated a significant correlation between dryness rate and both patients' age (negative) and bladder compliance (positive). Several uncontrolled or comparative studies provided significative evidence of the clinical benefit and safety of BoNT-A administration in children in terms of UI relief and improvement of urodynamic parameters, with neurogenic aetiologies being the most investigated conditions. A reduced bladder compliance was identified as one of the potential predictors of poor response to BoNT-A. Moreover, the earlier the treatment was started the higher the success rate that was reached in terms of dryness/urinary continence achievement.

Impact of MicroRNA Depletion on Maintenance of Adult Bladder Urothelium

Impact of MicroRNA Depletion on Maintenance of Adult Bladder Urothelium

Acupuncture for overactive bladder in adults: Study protocol for a randomized controlled trial

BackgroundOveractive bladder (OAB) is a prevalent condition that substantially degrades patient quality of life. Acupuncture is recognized as an effective therapeutic approach for various urological diseases. However, there is limited evidence validating the effectiveness and safety of acupuncture for OABs. ObjectiveTo assess the therapeutic efficacy of acupuncture for OAB and to investigate the potential mechanisms by analyzing its effects on relevant urinary biomarkers. MethodsThis is a randomized, participants and outcome assessors blinded, sham acupuncture controlled trial. A total of 110 patients with OABs will be randomly divided in a 1:1 ratio between the acupuncture and sham acupuncture groups. Participants in the acupuncture group will undergo 30-min authentic acupuncture, while their counterparts in the sham acupuncture group will undergo sham acupuncture needling non-acupoints superficially three times weekly for a duration of 8 weeks. The two co-primary outcomes will be the change in the mean number of micturitions per 24 h from baseline to the end of the 8-week treatment and 20-week follow-up. The secondary outcomes will encompass the change in Overactive Bladder Symptom Score, Overactive Bladder Questionnaire Short Form, and average 24 h values of urgency, daytime micturition, nocturia, and mean volume voided per micturition from baseline to weeks 8 and 20. Urinary nerve growth factor, brain-derived neurotrophic factor, and monocyte chemoattractant protein-1 levels will be measured at baseline and week 8. Adverse events will also be documented. DiscussionThe results of this trial will provide evidence for the effectiveness and safety of acupuncture in the management of OAB.

Association Between Proton Pump Inhibitor Use and Overactive Bladder Risk in Adults: A Cross-sectional Study

ObjectivesTo investigate the association between the use of Proton Pump Inhibitors (PPIs) and Overactive Bladder (OAB) in adults. MethodsThis study adopts a cross-sectional approach to scrutinize data derived from the National Health and Nutrition Examination Survey (NHANES), spanning from 2007 to 2018. It employs multivariable logistic regression along with restricted cubic splines (RCS) to investigate the relationship between the use of PPI and the incidence of OAB. Additionally, through interaction and stratification analyses, the study delves into how specific factors may influence this correlation. ResultsA total of 24,458 adults participated in this study. Individuals using PPIs exhibited higher rates of nocturia, urge incontinence, and OAB compared to non-users. After full adjustment, PPI users had a significantly increased risk of developing OAB (OR = 1.36, 95%CI: 1.17-1.60). Moreover, with each year of continued PPI usage, the frequency of OAB symptoms escalated by 3% (p=0.01). Further examinations within various subgroups maintained a uniform direction in these effect estimates. ConclusionsThe findings of this research highlight a noteworthy positive link between the use of PPIs and the emergence of OAB among adults. Moreover, it was observed that an extended period of using PPIs correlates with a heightened likelihood of encountering OAB.

Continent stoma with Modified Mansoura Technique (Indiana W pouch with nipple valve fixation) in adult bladder exstrophy: A rare case report on step-by-step surgery technique and outcome

Introduction: Bladder exstrophy (BE), a complex and severe congenital defect of urogenital sinus and the musculoskeletal system, in adulthood is very rare. The surgical management of adulthood bladder exstrophy is complex and post operative complications are possible. This case report show surgical management step-by-step and post operative outcomes of neglected bladder exstrophy with contracted bladder, right renal agenesis, bilateral unpalpable undescended testis (UDT), and megarecti with scibala. Case Presentation: A 23 years old male with neglected bladder exstrophy with contracted bladder, right renal agenesis, bilateral unpalpable undescended testis (UDT), and megarecti with scibala underwent Modified Mansoura Technique (Indiana W pouch + Nipple valve fixation) for the bladder exstrophy, orchidopexy with Shehata technique. Conclusion: Modified Mansoura Technique (Indiana W pouch + Nipple valve fixation) approach yielded favorable outcomes without post operative complications, at least during the monitoring period in hospital. However, continued follow-up is necessary to ensure long-term success.

Bladder training for treatment of overactive bladder in adults

Bladder training for treatment of overactive bladder in adults

Small cell neuroendocrine carcinoma and poorly differentiated rhabdomyosarcomas of the urinary bladder in adults—A comparative analysis in favor of a common histogenesis

Rhabdomyosarcoma (RMS) of the urinary bladder in adults and elderly is an exceptionally rare neoplasm that displays poorly differentiated solid (alveolar-like) small cell pattern, frequently indistinguishable from small cell neuroendocrine carcinoma (SCNEC). However, the histogenesis of RMS and SCNEC and their inter-relationship have not been well studied and remained controversial. We herein analyzed 23 SCNEC and 3 small round cell RMS of the bladder for neuroendocrine (synaptophysin + chromogranin A) and myogenic (desmin + myogenin) marker expression and for TERT promoter mutations. In addition, the RMS cohort and one SCNEC that was revised to RMS were tested for gene fusions using targeted RNA sequencing (TruSight Illumina Panel which includes FOXO1 and most of RMS-related other genes). Overall, significant expression of myogenin and desmin was observed in one of 23 original SCNEC justifying a revised diagnosis to RMS. On the other hand, diffuse expression of synaptophysin was noted in 2 of the 4 RMS, but chromogranin A was not expressed in 3 RMS tested. TERT promoter mutations were detected in 15 of 22 (68%) SCNEC and in two of three (67%) assessable RMS cases, respectively. None of the four RMS cases had gene fusions. Our data highlights phenotypic and genetic overlap between SCNEC and RMS of the urinary bladder. High frequency of TERT promoter mutations in SCNEC is in line with their presumable urothelial origin. In addition, the presence of TERT promoter mutation in 2 of 3 RMS and lack of FOXO1 and other gene fusions in all 4 RMSs suggest a mucosal (urothelial) origin, probably representing extensive monomorphic rhabdomyoblastic transdifferentiation in SCNEC.

Keratin 5 basal cells are temporally regulated developmental and tissue repair progenitors in bladder urothelium.

Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical, and bacterial injuries. Biochemical and genetic labeling studies support the existence of one or more progenitor populations with the capacity to rapidly regenerate the urothelium following injury, but slow turnover, a low mitotic index, and inconsistent methodologies obscure progenitor identity. The progenitor properties of basal keratin 5 urothelial cells (K5-UCs) have been previously investigated, but those studies focused on embryonic or adult bladder urothelium. Urothelium undergoes desquamation and apoptosis after birth, which requires postnatal proliferation and restoration. Therefore, we mapped the fate of bladder K5-UCs across postnatal development/maturation and following administration of cyclophosphamide to measure homeostatic and reparative progenitor capacities, respectively. In vivo studies demonstrate that basal K5-UCs are age-restricted progenitors in neonates and juveniles, but not in adult mice. Neonatal K5-UCs retain a superior progenitor capacity in vitro, forming larger and more differentiated urothelial organoids than adult K5-UCs. Accordingly, K5-UC transcriptomes are temporally distinct, with enrichment of transcripts associated with cell proliferation and differentiation in neonates. Induction of urothelial proliferation is sufficient to restore adult K5-UC progenitor capacity. Our findings advance the understanding of urothelial progenitors and support a linear model of urothelial formation and regeneration, which may have significant impact on therapeutic development or tissue engineering strategies.NEW & NOTEWORTHY Fate mapping reveals an important linear relationship, whereby bladder basal urothelial cells give rise to intermediate and superficial cells in an age-restricted manner and contribute to tissue repair. Neonatal basal cells reprise their role as superior progenitors in vitro and display distinct transcriptional signatures, which suggest progenitor function is at least partially cell intrinsic. However, the urothelium progenitor niche cannot be overlooked, since FGF7 rescues adult basal cell progenitor function.

Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

Vibegron is a selective β3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

An Analysis of the Efficacy of Multilayered Repair and Reconstruction Using Combined Tissue Pedicle Flaps for Abdominal Wall Defects in Adult Bladder Exstrophy Patients.

In this study, we conducted a retrospective analysis of cases involving adult classic bladder exstrophy (CBE) accompanied by the absence of the abdominal wall. Specifically, we focused on the utilization of multilayer flaps for reconstructive purposes. In addition, we aimed to share our clinical treatment experience pertaining to similar challenges, thereby providing valuable insights to complement the surgical management of this rare disease. We conducted a retrospective analysis of 12 adult patients diagnosed with CBE who underwent initial treatment between June 2013 and January 2020. All patients underwent multilayer reconstruction to address their abdominal wall defects. This involved utilizing shallow flaps derived from the superficial fascia of the abdomen and incorporating myofascial flaps composed of the anterior sheath of the rectus abdominis and aponeurosis of the external oblique muscle. The flap sizes ranged from 9 × 11 cm to 13 × 15 cm. Abdominal wall reconstruction in the 12 patients with CBE resulted in an absence of wound dehiscence recurrence, urinary obstruction, or urinary tract infection. All patients expressed satisfaction with the aesthetic outcome of their abdominal wall based on self-evaluation. They reported a successful resumption of normal life and work activities without experiencing any restrictions. The married patients expressed contentment with their sexual function. The utilization of a multilayered reconstruction technique involving multiple flaps in adults with congenital CBE allows for successful restoration of urinary function, as well as the attainment of sufficient abdominal wall strength to support daily life and work activities, while preserving sexual function. However, it is important to approach the evaluation of surgical outcomes with caution because of the rarity of this condition and the lack of objective assessment measures.

Urachal cyst as a rare case involving urinary bladder in adults: A case report

Urachal cyst as a rare case involving urinary bladder in adults: A case report

Embryonal Rhabdomyosarcoma of the Bladder in Adults: A Case Report and Comprehensive Literature Review

Embryonal Rhabdomyosarcoma of the Bladder in Adults: A Case Report and Comprehensive Literature Review

Distinct effects of Fgf7 and Fgf10 on the terminal differentiation of murine bladder urothelium revealed using an organoid culture system

BackgroundDysregulation of the terminal differentiation of bladder urothelium is associated with the pathogenesis of urinary tract disorders. Fibroblast growth factor (Fgf)7 and Fgf10 stimulate urothelial proliferation; however, their roles in cellular differentiation remain unclear. In this study, we used an organoid system to investigate the roles of these Fgfs in regulating bladder urothelium differentiation and identify their distribution patterns in the mouse bladder.MethodsAdult bladder epithelia (AdBE) isolated from adult mouse bladder tissues (AdBTs) were used to culture adult bladder organoids (AdBOs) in the presence of Fgf7 and Fgf10. The differentiation status of the cells in AdBTs, AdBEs, AdBOs, and neonatal bladder tissues (NeoBTs) was analyzed via quantitative real-time-PCR for the presence of undifferentiated cell markers (Krt5, Trp63, and Krt14) and differentiated cell markers (Krt20, Upk1a, Upk2, and Upk3a). Organoid cell proliferation was assessed by counting cell numbers using the trypan blue method. The effects of Fgf7 and Fgf10 on organoid differentiation were assessed using different doses of Fgfs, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) signaling in these processes was tested by introducing a PPARγ agonist (Rosiglitazone) and antagonist (T0070907) to the culture. The expression patterns of Fgf7 and Fgf10 were examined via in situ hybridization of AdBTs.ResultsAdBOs showed higher expression of undifferentiated cell markers and lower expression of differentiated cell markers than AdBTs, NeoBTs, and AdBEs, indicating the relatively immature state of AdBOs. Differentiation of AdBOs was enhanced by Rosiglitazone and Fgf7, suggesting an interplay of intracellular signals between Fgf7 and PPARγ. Co-addition of T0070907 suppressed Fgf7-mediated differentiation, demonstrating that PPARγ is activated downstream of Fgf7 to promote cellular differentiation into umbrella cells. Furthermore, we found that Fgf7 is predominantly expressed in the umbrella cells of the urothelium, whereas Fgf10 is predominantly expressed in the urothelium and stroma of AdBTs.ConclusionsWe demonstrated that unlike Fgf10, Fgf7 induces cellular differentiation via PPARγ activity and has a unique tissue distribution pattern in the adult bladder. Further studies on the Fgf7-PPARγ signaling axis would provide insights into the differentiation mechanisms toward functional umbrella cells and the pathogenesis of several urinary tract diseases.

Transitioning young adults with spina bifida: Challenges and paths to success

Recent medical advances, including closure of myelomeningocele defects, shunting of hydrocephalus, and focusing on renal preservation have led to many individuals with spina bifida (SB) living into adulthood. This has led to more individuals with SB transitioning their care from pediatric-based to adult-based care models. We seek to explore the process of transition, with a focus on difficulties in transitioning individuals with SB. Additionally, we explore new problems that arise during the period of transition related to sexual function and dysfunction. We also discuss some of the difficulties managing neurogenic bladder and the sequalae of their prior urologic surgeries. Each of the authors was asked to provide a summary, based on current literature, to highlightthe challenges faced in their area of expertise. Transitioning care for individuals with SB is especially challenging due to associated neurocognitive deficits and neuropsychological functioning issues.Sexual function is an important component of transition that must be addressed in young adults with SB. Management of neurogenic bladder in adults with SB can be challenging due to the heterogeneity of the population and the sequelae of their prior urologic surgeries. The aim is to ensure that all individuals with SB receive appropriate, evidence-based care throughout their lifetime.

The Role of Sarcopenia in Overactive Bladder in Adults in the United States: Retrospective Analysis of NHANES 2011-2018.

To investigate the association between sarcopenia and overactive bladder (OAB) in a United States adult population from 2011 to 2018, and whether sarcopenia can predict the risk of OAB. We analyzed data from the 2011-2018 National Health and Nutrition Examination Survey in a cross-sectional study(NHANES) of 8746 participants, of whom 1213 were diagnosed with OAB, we analyzed correlations by sex, age, race, education level, marital status, household income-to-poverty ratio, hypertension, diabetes, strenuous work activity, moderate work activity, strenuous recreational activity, moderate recreational activity, blood urea nitrogen, creatinine, and uric acid levels using restricted cubic spline plots of dose-response curves, univariate and multivariate Logistic regression. Models based on sex, age, education, household income to poverty ratio, hypertension, diabetes, sarcopenia index, and cotinine were developed and evaluated using Nomogram, calibration curves, receiver operating characteristic curves, and clinical decision curves. Of the 1213 OAB patients, 388 (32.0%) were male and 825 (68.0%) were female. Univariate and multivariate Logistic regression analysis showed that sarcopenia index was negatively correlated with the prevalence of OAB (OR=0.084, 95% CI, 0.056 - 0.130, P <0.001;OR=0.456, 95%CI, 0.215-0.968, P= 0.0041). Dose curve analysis of the sarcopenia index and prevalence of OAB showed that the prevalence of OAB decreased significantly with increasing sarcopenia index. Sarcopenia was positively correlated with OAB (OR=2.400, 95%CI, 2.000 - 2.800, P <0.001;OR=1.46, 95%CI, 1.096 -1.953, P = 0.010). In addition, our model shows that sarcopenia can predict the prevalence of OAB (AUC = 0.750) and has some clinical decision-making implications. Sarcopenia is positively associated with the risk of OAB in United States adults and can be used as a predictor of OAB prevalence.

Hypoxanthine Induces Signs of Bladder Aging With Voiding Dysfunction and Lower Urinary Tract Remodeling.

Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX-ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging. Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg/kg/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed. HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence). These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions.