Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics

Introduction and hypothesis

The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E₂ (PGE₂) in women with overactive bladder (OAB) following anticholinergic treatment.

Methods

A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE₂ levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared.

Results

Urinary NGF and PGE₂ levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE₂ levels were not significantly different between pre- and post-treatment in either group.

Conclusions

NGF and PGE₂ have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.     

Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVE

To compare urinary nerve growth factor (NGF) and prostaglandin E2 (PGE2) levels among patients with detrusor overactivity (DO), increased bladder sensation (ISB), interstitial cystitis/bladder pain syndrome(IC/BPS) and controls.

PATIENTS, SUBJECTS AND METHODS

Urine samples were collected from 40 women with IC/BPS, 54 with overactive bladder (OAB) and 27 normal women as controls, all with a full bladder. Patients with OAB were further classified into subgroups of DO or IBS by urodynamic results. Urinary NGF and PGE2 levels were measured using an enzyme‐linked immunosorbent assay. Urinary NGF and PGE2 levels were normalized by urinary creatinine (Cr) levels and compared among all subgroups.

RESULTS

Urinary NGF levels were increased in the 40 women with IC/BPS and 23 with DO but not in 31 with IBS and the 27 controls. Mean (sd ) urinary NGF/Cr levels were not significantly different between patients with IC/BPS, at 1.35 (0.36), and DO, at 1.93 (0.77). Urinary NGF/Cr levels were significantly higher in women with IC/BPS than in women with IBS, at 0.25 (0.10) (P = 0.01). Using receiver operating characteristic curves for assessing urinary NGF/Cr levels in patients with IC/BPS and IBS, IC/BPS was diagnosed with a sensitivity and specificity of 75% and 65.5%, respectively, based on a urinary NGF/Cr threshold of 0.015. However, urinary PGE2/Cr levels were not significantly different among all subgroups.

CONCLUSIONS

Urinary NGF/Cr levels are elevated in women with IC/BPS or DO, but not in those with IBS. The differential diagnosis of women with IC/BPS from those with frequency‐urgency syndrome is possible based on urinary NGF/Cr levels but not urinary PGE2/Cr level.     

Changes in nerve growth factor level and symptom severity following antibiotic treatment for refractory overactive bladder

Introduction and hypothesis

Overactive bladder (OAB) has a multifactorial aetiology, and for some women symptoms may be associated with chronic urothelial inflammation secondary to bacterial colonisation. One marker of such inflammation may be urinary nerve growth factor (NGF). We hypothesised that for women with OAB and urothelial inflammation, urinary NGF would be reduced following antibiotic therapy.

Methods

Women with overactive bladder and urodynamic diagnosis of detrusor overactivity who were refractory to anticholinergics, and had histological evidence of urothelial inflammation were treated with a 6-week course of rotating antibiotics. Urinary NGF was measured by ELISA before and after treatment. Three-day bladder diaries, the Patients’ Perception of Intensity of Urgency Scale, the King’s Health Questionnaire and the Patients’ Perception of Bladder Condition questionnaire were used to assess subjective and objective outcomes of therapy.

Results

Thirty-nine women with refractory DO were recruited. The NGF levels decreased significantly after antibiotic therapy (Wilcoxon signed rank test; p?=?0.015). There were significant improvements in daytime frequency, nocturia and urgency (p?<?0.05), and 74 % of women reported improvement in perception of their bladder condition.

Conclusions

Urinary NGF is responsive to antibiotic therapy. Women with refractory overactive bladder and elevated NGF may benefit from antibiotic treatment.     

Urinary brain-derived neurotrophic factor: a potential biomarker for objective diagnosis of overactive bladder

Purpose

To investigate the diagnostic performance of urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) as potential biomarkers for overactive bladder (OAB).

Methods

Ninety women diagnosed with OAB and 45 normal controls without OAB were enrolled. Urine samples were collected from all subjects. Urinary BDNF and NGF levels were measured using enzyme-linked immunosorbent assays. Results normalized by urinary creatinine (Cr) levels were compared between OAB groups and controls. Symptom severity was assessed using overactive bladder symptom score.

Results

Urinary BDNF and NGF levels were elevated in OAB groups but not in controls. Mean (SD) baseline BDNF and NGF levels normalized by Cr levels were significantly higher in OAB subjects than in controls (20.609 ± 23.932 vs. 1.779 ± 0.729, p < 0.01) and (0.258 ± 0.264 vs. 0.081 ± 0.028, p < 0.01), respectively. Urinary BDNF/Cr levels were 80-fold higher than NGF/Cr levels in OAB subjects. Receiver operating characteristic curves for assessing urinary BDNF/Cr levels in OAB groups showed sensitivity and specificity of 93.33 and 88.89 %, respectively. Urinary BDNF levels were associated with OAB symptom severity.

Conclusions

Urinary BDNF/Cr levels are elevated in women with OAB and are significantly associated with symptom severity. No elevation of BDNF is found in women without OAB. BDNF analysis has better sensitivity than NGF in detecting OAB in subjects without other lower urinary tract disorders. Results of the present study suggest a potential role for BDNF as an objective biomarker for OAB diagnosis.     

Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment

OBJECTIVE

To measure urinary nerve growth factor (NGF) levels in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), and to evaluate the role of urinary NGF in predicting the response to treatment, as the clinical diagnosis of IC/BPS is based on subjective symptoms and recent investigations suggest that urinary NGF is increased in patients with IC/BPS.

PATIENTS, SUBJECTS AND METHODS

Urine samples from 122 patients with IC/BPS and 28 normal controls were measured for NGF levels using an enzyme‐linked immunosorbent assay. The diagnosis of IC/BPS was based on bladder pain symptoms and the results of cystoscopic hydrodistension. Patients’ perception of pain was assessed by a visual analogue scale (VAS) and a ‘global’ response assessment after treatment. Urinary NGF levels were further normalized to the concentration of urinary creatinine (NGF/Cr) and compared between control and IC/BPS subgroups at diagnosis and after treatment.

RESULTS

Urinary NGF/Cr levels were very low when the bladder was not distended and significantly elevated with a full bladder in patients with IC/BPS. However, urinary NGF/Cr levels were not correlated with VAS scores or cystometric bladder capacity at diagnosis, or maximum bladder capacity during hydrodistension. Patients who responded to treatment and had an improvement in VAS pain score of ≥2 had significantly lower NGF/Cr levels than nonresponders who had a VAS improvement of <2.

CONCLUSIONS

Patients with IC/BPS had greater urinary NGF/Cr levels than controls. A decrease of urinary NGF level was associated with greater pain reduction and a successful response, suggesting that urinary NGF levels can be a useful biomarker for detecting the severity of the bladder condition in patients with IC/BPS.     

Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C

Introduction and hypothesis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner’s lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found.

Methods

Cold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups.

Results

High expression of T- and B-cell markers (CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers (KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls.

Conclusions

BPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C.     

Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic pelvic pain: a prospective observational study

Introduction and hypothesis

This study assesses the prevalence of interstitial cystitis (IC)/bladder pain syndrome (BPS) in women with chronic pelvic pain (CPP).

Methods

This was a prospective study of 150 women undergoing laparoscopy as investigation for CPP in an Endometriosis and Pelvic Pain unit. Preoperative questionnaires [demographic details, pelvic pain symptoms, the Pelvic Pain and Urgency/Frequency (PUF) and O’Leary-Sant (OLS) Symptom and Problem Index scores] were completed, and concurrent standardized cystoscopy with hydrodistention performed at laparoscopy. The primary outcome measures the proportion of IC in this group, defined by presence of glomerulations with CPP and urinary symptoms (urinary frequency, nocturia, urgency). The secondary outcome measures the proportion of BPS [defined by the European Society of the Study of Interstitial Cystitis (ESSIC)].

Results

IC was diagnosed in 48/150 (32%) individuals, and 80/150 (53%) had BPS. There were no significant differences in symptomatology or questionnaire results between groups with and without IC. Women with BPS had higher PUF (17.2 vs 12.9, p?p?=?0.001) and Problem (7.5 vs 4.2, p?Conclusions The prevalence of IC/BPS varies depending on the definition used. This study showed IC in 32% of women with CPP based on symptoms and presence of glomerulations. BPS as defined by ESSIC was diagnosed in 53%. History and questionnaires did not correlate with positive cystoscopic findings.     

Urinary nerve growth factor in women with overactive bladder syndrome

Study Type – Aetiology (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Urinary nerve growth factor levels were higher in women with OAB‐dry and OAB‐wet compared to the controls. The link between female OAB and risk factors such as obesity and menopause has not been determined yet. This study found ageing, menopause, or higher BMI did not influence the urinary NGF levels in OAB women. Higher urinary NGF levels in OAB women could be an inflammatory disorder unrelated to ageing or obesity.

OBJECTIVE

? To measure urinary nerve growth factor (NGF) in women with overactive bladder (OAB)‐dry and OAB‐wet and investigate the association of urinary NGF expression with these factors.

PATIENTS AND METHODS

? Differentiation between OAB‐wet and OAB‐dry was based on symptoms and a 3‐day voiding diary. ? Urinary NGF levels were measured by enzyme‐linked immunosorbent assay (ELISA). ? The urinary NGF levels were compared among controls, OAB‐dry and OAB‐wet subgroups, and also between OAB patients ≥55 years and <55 years, as well as between patients with a body mass index (BMI, kg/m²) <20, 20–30 and >30.

RESULTS

? A total of 113 women with OAB‐dry, 106 with OAB‐wet and 84 controls were enrolled. The urinary NGF/creatinine (Cr) levels were significantly highest in OAB‐wet (2.13 ± 3.87) and second highest in OAB‐dry (0.265 ± 0.59) compared to controls (0.07 ± 0.21). ? Analysis of urinary NGF or NGF/Cr levels among controls, OAB‐dry and OAB‐wet groups by age and BMI showed no significant differences, except for the OAB‐dry group. ? Urinary NGF/Cr was not significantly correlated with age (P= 0.088) or BMI (P= 0.886) in women with OAB‐dry and OAB‐wet.

CONCLUSIONS

? Urinary NGF levels were significantly higher in women with OAB‐dry and even higher in women with OAB‐wet. ? The urinary NGF level was not associated with ageing, menopause or higher BMI either in controls or OAB patients.     

Association of inflammaging (inflammation + aging) with higher prevalence of OAB in elderly population

Introduction

Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients.

Methods

Single time point urine specimens were obtained from 140 OAB patients in the age range of 25–90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients.

Results

In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112–0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort.

Conclusions

Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients.     

The role of serum C-reactive protein in women with lower urinary tract symptoms

Introduction and hypothesis

Some lower urinary tract dysfunction (LUTD) subtypes may be associated with low-grade inflammation. This study aimed to investigate the role of serum C-reactive protein (CRP) levels in women with lower urinary tract symptoms (LUTS).

Methods

A total of 197 consecutive women with non-stress urinary incontinence (non-SUI) LUTS and 18 healthy women without LUTS (normal controls) were enrolled. LUTS include urinary storage, voiding, and post-micturition symptoms. Patients with previous bladder or urethral surgery, active urinary tract infections, or possible neurogenic lesions were excluded. Serum CRP levels were measured before any treatment was given. Patients were stratified to LUTD subgroups based on a 3-day voiding diary, uroflowmetry, and selective videourodynamic studies.

Results

Median CRP levels were significantly higher in women with overactive bladder (OAB) wet (i.e., with urgency incontinence, n?=?30, 0.12 mg/dl) than those in women with bladder oversensitivity (n?=?68, 0.075 mg/dl, P?=?0.008) and the control group (0.055 mg/dl, P?=?0.032). Further analysis revealed that body mass index and maximum flow rate were two independent factors that affected CRP levels. The area under the receiver-operating characteristic curve for using CRP to predict OAB wet was 0.55, and the most predictive cutoff point for CRP was 0.15 mg/dl (sensitivity 43.5 %, specificity 72.7 %).

Conclusions

High serum CRP levels were found in women with OAB wet, and they were related to lower maximum urinary flow rates and higher body mass indices in non-SUI LUTD. However, serum CRP is not a suitable biomarker for discriminating between subtypes of non-SUI LUTD.     

Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC)

Purpose

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor.

Methods

Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n?=?44; age 60.64?±?13.78, mean?±?SD) and carcinoma patients (n?=?11; age 58.91?±?12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1–3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR).

Results

M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2?>?M3 and M3?>?M2) were observed, which differed in associated purinergic and histamine receptor expression.

Conclusions

M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.     

Pain and embarrassment associated with urodynamic testing in women

Introduction

Multichannel urodynamics is a series of interactive tests used to evaluate lower urinary tract dysfunction. We sought to describe symptoms and satisfaction in a cohort of women undergoing these procedures.

Methods

Females undergoing urodynamics completed questionnaires immediately (Q1) and 1 week (Q2) after their testing. Surveys utilized visual analog scales (VAS) from 0 to 10 to assess pain, embarrassment, anxiety, and satisfaction. Q2 also inquired about urinary symptoms in the days following the procedure.

Results

100 women were analyzed. Regarding symptoms on the day of testing, VAS scores indicated low bother; with a median of 1.5/10 for pain, 0.4/10 for embarrassment, and 1.8/10 for anxiety. One week following, recall of pain (p?=?0.169), and embarrassment (p?=?0.722) were similar. Further analyses suggested that overactive bladder syndrome (OAB) might be associated with greater pain during and after the procedure (p?=?0.04, p?=?0.038 respectively), while depression was associated with greater embarrassment at those times (p?=?0.018, p?=?0.027 respectively). Painful bladder syndrome (PBS) was associated with a higher recall of pain (p?=?0.018), and anxiety with more embarrassment (p?=?0.033) on the second survey. Finally, younger age correlated with higher pain on both questionnaires (Q1: τ?=???0.148, p?=?0.029; Q2: τ?=???0.171, p?=?0.014). Following urodynamics, urgency was most common (43 %), generally resolving within 1 day. Reassuringly, 86 % would repeat urodynamics if necessary, and overall satisfaction was rated ≥9/10 at both time points.

Conclusion

Urodynamic testing is well-tolerated in women. Nevertheless, younger age, anxiety or depression, and a diagnosis of OAB and PBS may lead to more negative experiences. Such information may be useful in counseling future patients.     

Clinical and urodynamic differences among women with overactive bladder according to the presence of detrusor overactivity

Introduction and hypothesis

We tried to determine whether clinical and urodynamic differences exist between women with and without detrusor overactivity (DO) using a large database of overactive bladder (OAB) patients.

Methods

We reviewed the medical records of 513 women who underwent urodynamic studies for OAB symptoms without neurogenic or anatomical conditions that affect micturition function. Clinical symptoms were evaluated using a 3-day frequency-volume chart (FVC) including the Urinary Sensation Scale and American Urological Association Symptom Index (AUA-SI). All clinical and urodynamic findings were compared between women with and without DO.

Results

The patients’ mean age was 58.9 years. DO was identified urodynamically in 167 (32.6 %) women. Those with DO were older (62.9 vs 57.0 years, p?<?0.001); however, no differences in AUA-SI, episodes of daytime voiding, and episodes of nocturia were observed between the groups. Functional bladder capacity was smaller in women with DO; however, this difference did not reach statistical significance. Women with DO had significantly more urgency incontinence symptoms than those without DO (55.1 vs 29.5 %, p?<?0.001). In urodynamic parameters, the volumes at first desire to void and strong desire to void and maximum cystometric capacity were significantly smaller, and detrusor pressure at the opening was significantly higher in women with DO compared to subjects without DO (26.2 vs 21.2 cmH₂O, p?=?0.004).

Conclusions

Our findings suggest a more severe disturbance of bladder function when DO exists, although no differences were observed in symptom scores and 3-day FVC parameters among women with OAB symptoms according to the presence of DO.     

Wertigkeit des ?nerve growth factor“ beim Syndrom der überaktiven Blase

Objectives

Several studies discussing the pathology of overactive bladder suggested changes in urinary proteins. The neurotrophin “nerve growth factor” (NGF) seems to be an important marker in overactive bladder syndrome (OAB). In this prospectively designed study we evaluated NGF blood levels (sNGF) initially and after injection of botulinum toxin type A (BTX-A) in the detrusor muscle in patients suffering from idiopathic OAB.

Materials and methods

Blood samples were obtained from 26 patients (66.5 years, 28–83) with idiopathic OAB. sNGF levels were measured before and 4 weeks after BTX-A treatment by enzyme-linked immunosorbent assay (ELISA). A group of 32 healthy persons with normal bladder function served as controls (41 years, 19–60). sNGF was evaluated in relation to clinical data and the severity of OAB (wet/dry).

Results

Significantly higher sNGF levels were detected in patients with OAB compared to the control group (58.8 vs 2.0 pg/ml, p<0.005). Further, sNGF levels were elevated in patients with wet OAB compared to patients with dry OAB (85.0 vs 0.73 pg/ml, p<0.005). Patients > 60 years showed significantly higher sNGF levels (77.2 vs 8.9 pg/ml, p<0.05) compared to younger OAB patients. After BTX-A therapy sNGF levels decreased significantly compared to baseline (p<0.005).

Conclusion

NGF appears to play a decisive role in OAB. Its use as a biomarker in both the diagnostics and follow-up after therapy seems promising. To what extent sNGF can be useful as a biomarker or in therapy monitoring needs to be examined prospectively in a larger population.     

Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder

OBJECTIVE

To determine urinary nerve growth factor (NGF) levels in patients with overactive bladder (OAB) and after treatment with antimuscarinics.

PATIENTS AND METHODS

Urinary NGF levels were measured in 38 ‘normal’ controls and 70 patients with OAB. Patients were treated with tolterodine 4 mg once daily. Urinary NGF levels were measured by enzyme‐linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cr). The urinary NGF/Cr levels and urgency severity scale (USS) were compared at baseline, 1, 2 and 3 months after antimuscarinics, and 1 month after discontinuing treatment.

RESULTS

The urinary NGF/Cr level was very low in normal controls with a mean (sem ) of 0.005 (0.003). Patients with OAB had significantly higher baseline urinary NGF/Cr levels than the controls. Urinary NGF/Cr levels were significantly reduced at 3 months in 50 responders (1.10 [0.26] before vs 0.41 [0.09] after, P = 0.008) but not in the 20 non‐responders (1.38 [0.54] before vs 1.30 [0.46] after, P = 0.879). However, after discontinuing antimuscarinic treatment for 1 month, the urinary NGF/Cr level was elevated in 23 responders at 0.83 (0.33) and in five non‐responders at 2.72 (1.41). The USS scores significantly changed with the change of urinary NGF/Cr levels in responders at different time points. The voided volume increased but maximum urinary flow rate and postvoid residual volume did not increase in responders after 3‐months of antimuscarinic treatment. The limitation of this study was the lack of a control arm for comparison.

CONCLUSIONS

Changes in the urinary NGF levels were associated with the changes of the USS scores after antimuscarinic treatment and discontinued medication. The urinary NGF level could be a potential biomarker for evaluating therapeutic results of antimuscarinics therapy.     

Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis

Introduction and hypothesis

Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods

Twenty-two patients with IC/BPS received intravesical instillations (40?ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL?, IBSA) once weekly for 8?weeks, then once every 2?weeks for the next 6?months.

Results

The score for urgency was reduced from 6.5 to 3.6 (p?=?0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p?=?0.0001). The average urine volume increased from 129.7 to 162?ml (p?p?p?p?Conclusion The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.     

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC)

Purpose

Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls.

Methods

Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction.

Results

We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients.

Conclusions

The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.     

A multicentre,prospective, randomised,double-blind study to measure the treatment effectiveness of abobotulinum A (AboBTXA) among women with refractory interstitial cystitis/bladder pain syndrome

Introduction and hypothesis

To determine if abobotulinumtoxin A (AboBTXA) is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods

We performed a double-blind study of 54 women with severe, refractory IC from three referral centres whom we randomly allocated to treatment with hydrodistension + injection of normal saline or to hydrodistension + injection with AboBTXA. The O’Leary-Sant questionnaire consists of problem (OLS-PI) and symptom (OLS-PI) index scores, and bladder diary data were compared between AboBTXA and control patients at baseline and at 3 months of follow-up. Measurements were made beyond 3 months, but no further randomised comparison was possible due to the ability of nonresponsive patients in either group to have AboBTXA treatment.

Results

Complete data were available in 50 patients, and in both groups, OLS questionnaires showed improvement at 3 months. Only the OLS-PI was improved in the AboBTXA group (p?=?0.04). At 3 months, no difference was found in either OLS-SI or total OLS score. Twelve patients had urinary tract infection (UTI) treated during the follow-up period, which confounded results. In the 38 patients without UTI, there was improvement in total OLS score (p?=?0.02), OLS-PI (0.08), and OLS-SI (p?=?0.008) for the AboBTXA group at 3 months. Only five AboBTXA compared with two control patients had a 50 % reduction in OLS score.

Conclusions

For chronic refractory IC/BPS patients, AboBTXA was associated with no overall improvement in total OLS score, although significant benefit was noted in a small number of patients. The absence of posttreatment UTI was associated with a better response to AboBTXA.     

Urinary nerve growth factor level could be a biomarker in the differential diagnosis of mixed urinary incontinence in women

OBJECTIVES

To measure urinary nerve growth factor (NGF) levels in women with stress urinary incontinence (SUI) and overactive bladder symptoms (OAB) and to assess whether urinary NGF levels can be a biomarker of detrusor overactivity (DO) in women with mixed urinary incontinence.

PATIENTS, SUBJECTS AND METHODS

Urinary NGF levels were measured in 38 women with urodynamic SUI (USI) with OAB, in 26 with urodynamic DO but no SUI, in 21 with persistent USI after anti‐incontinence surgery, in 15 with de novo DO, and in 31 normal control subjects. All participants had a video‐urodynamic study for the differential diagnosis of the underlying causes of UI. Urinary NGF levels were measured using an enzyme‐linked immunosorbent assay and were compared among all subgroups, and corrected using urinary creatinine (Cr) levels.

RESULTS

The mean (sem ) urinary NGF/Cr levels were low both in controls, at 0.06 (0.004) and in women with pure USI, at 0.056 (0.037) (P = 0.108). The NGF/Cr levels were significantly higher in women with mixed USI and DO, at 1.00 (0.244), than in controls (P < 0.001) and those with pure USI (P = 0.006), but were similar to the levels in women with pure DO, at 0.58 (0.17) (P = 0.058). The NGF/Cr levels were undetectable in women with persistent USI but were significantly higher in those with de novo DO, at 2.39 (0.90), after anti‐incontinence surgery than in controls and those with USI. A urinary NGF/Cr level of >0.05 was found in 9% of women with USI, 77% with DO, 81% with mixed USI and DO, and 80% with de novo DO.

CONCLUSION

The urinary NGF level could be a potential biomarker of DO in women with mixed UI.