Urinary Nerve Growth Factor Levels Research Articles

Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a β3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. Urinary NGF and BDNFlevels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

Urinary biomarkers in children with neurogenic and non-neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD). The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program. A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges's g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001). Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD.

Discriminating Different Bladder and Bladder Outlet Dysfunctions by Urinary Biomarkers in Women with Frequency–Urgency Syndrome

To investigate the role of urinary biomarkers in discriminating different bladder and bladder outlet dysfunctions in women with frequency-urgency syndrome. Urine samples collected from 146 women with frequency-urgency syndrome and 34 controls were investigated. All patients were included in previous clinical trials of functional urology studies and underwent a videourodynamic study. Patients with frequency-urgency syndrome were subdivided into idiopathic detrusor overactivity (IDO), neurogenic detrusor overactivity (NDO), dysfunctional voiding (DV), and hypersensitive bladder (HSB) subgroups. Urine samples were collected before any treatment, and urinary inflammatory proteins (interleukin- (IL-) 1β, IL-2, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)), neurogenic proteins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin E2 (PGE2)), and oxidative stress biomarkers (8-isoprostane, total antioxidant capacity (TAC), and 8-hydroxydeoxyguanosine (8-OHdG)) were measured and compared between the different OAB subgroups and controls. Of the 146 patients, 31 had IDO, 41 had NDO, 45 had DV, and 29 had HSB. The control group included 34 women. The patients with HSB had lower urinary TAC and IL-2 levels than the controls. The patients with IDO, NDO, and DV had significantly higher urinary TNF-α levels than those with HSB. The patients with IDO and NDO showed an increase in the urinary 8-isoprostane levels, whereas the patients with IDO had higher urinary IL-2, NGF, and BDNF levels than those with NDO. The other urinary inflammatory biomarkers did not show enough significant differences to discriminate between the different bladder and bladder outlet dysfunctions. The urinary levels of inflammatory, neurogenic, and oxidative stress biomarkers varied widely among the patients with bladder and bladder outlet dysfunction. This study's results provide evidence that women with frequency-urgency syndrome and different urodynamic subtypes have varying bladder inflammation and oxidative stress conditions, which might have an impact on treatment outcomes.

Could urinary nerve growth factor and bladder wall thickness predict the treatment outcome of children with overactive bladder?

ABSTRACTObjective:Bladder wall thickness (BWTh) measurements and Nerve Growth Factor (NGF) /creatinine (Cr) values, as noninvasive tools, were found to predict daytime voiding problems in children with overactive bladder (OAB). The goal of this research was to examine if bladder wall thickness together with urine NGF/Cr could be a clinical utility in treatment outcome of OAB in children.Patients and Methods:A total of 60 children with OAB, (Group 1; n=40) and healthy normal controls (Group 2; n=20), aged 6-14 years old were involved in this prospective study. Children were evaluated with detailed history and physical examination, including neurologic examination, and were asked to complete a self-reported questionnaire and a 3-day bladder diary with the aid of their parents. Uroflowmetry was performed in all cases. Urinary nerve growth factor levels were measured by the ELISA and BWTh was measured trans-abdominally by one uro-radiologist specialized in pediatric ultrasonography. Urinary NGF levels were normalized by urinary creatinine levels and compared among all subgroups. Children with OAB received urotherapy as first line treatment at least for three months. 18 children refractory to urotherapy received anticholinergic therapy defined as group 3.Results:The median age of the study group was 10 (range 6 to 16). After urotherapy, 22 children had similar BWTh and NGF/Cr values compared to controls. (2.75 ± 1.15; 2.40 ± 1.00 mm; p=0.86 and 1.02 ± 0.10; 0.78 ± 0.15; p=0.12, respectively). After anticholinergic treatment, BWTh levels (2.25 ± 0.90; 2.40 ± 1.00 mm; p=0.94) and NGF/Cr values (0.95 ± 0.10; 0.78 ± 0.15; p=0.42, respectively) had no significantly difference compared to controls (Group 2).In receiver operating characteristic analysis, bladder wall thickness was found to have sensitivity of 85% and specificity of 84.2% (3,20 AUC, 913; 95 %) and NGF/Cr had sensitivity of 90% and specificity of 92.1% (1,595; AUC, 947; 95 %) in predicting treatment outcome in children with OAB.Conclusions:Bladder wall thickness measurements and NGF/Cr values, as noninvasive tools, could guide outcomes in the treatment of children with overactive bladder.

Plasma and Urinary Levels of Nerve Growth Factor Are Elevated in Primary Hypertension.

Nerve growth factor (NGF) is the main neurotrophic factor that can control sympathetic nerve innervation and sympathetic neural activity in cardiovascular organs. Although NGF overproduction and its influences on the sympathetic nervous system have been shown in hypertensive animals, NGF status and its association with sympathetic nerve activity have not yet been explored in human hypertension. In the present study, therefore, plasma and urinary levels of NGF and those of catecholamines (i.e., indices for NGF status and sympathoadrenal activity, respectively) were compared between 83 untreated primary hypertensives without apparent cardiovascular damages and 81 healthy normotensive subjects. Plasma and urinary levels of NGF were significantly greater in the hypertensive group (311 ± 158 pg/mL and 72.7 ± 54.0 ng/g of Cr) than in the normotensive group (168 ± 188 pg/mL and 54.5 ± 38.8 ng/g of Cr) (p < 0.05 for each measurement), even if the baseline differences of age and gender between the groups were adjusted. Similarly, plasma and urinary levels of catecholamines were significantly higher in the hypertensive group than in the normotensive group except for plasma noradrenaline. In addition, despite no significant correlations between plasma levels of NGF and catecholamines in both groups, urinary NGF significantly correlated positively with both urinary noradrenaline and urinary adrenaline in the hypertensive group (r = 0.259, p=0.018 and r = 0.232, p=0.035), but not in the normotensive group (r = 0.115, p=0.307 and r = −0.018, p=0.871). On the contrary, plasma and urinary levels of NGF as well as those of catecholamines did not associate with any systemic hemodynamic indices such as blood pressure and pulse rate in either group. Thus, primary hypertension was characterized by the enhancements of both NGF status and sympathoadrenal activity and the positive relationship between them. Our data indicate that enhanced NGF status and subsequent NGF-induced sympathoadrenal overactivity could occur in primary hypertension.

Urine Nerve Growth Factor May Not Be Useful as a Biomarker of Overactive Bladder in Patients with Pelvic Organ Prolapse.

(1) Background: Overactive bladder (OAB) symptoms are frequently present in women with pelvic organ prolapse (POP). Although urinary nerve growth factor (NGF) is a promising biomarker of OAB, little is known about its role in patients with OAB secondary to POP. The aim of the study was to evaluate urinary NGF levels in patients with POP involving the anterior vaginal wall and check if it may serve as a predicting factor for postoperative resolution of OAB symptoms. (2) Methods: Eighty-three Caucasian women included in the study were divided into three groups: pure OAB, one associated with POP (POP&OAB) and a control group composed of healthy volunteers. The urine NGF and creatinine were assessed with ELISA tests to calculate the NGF/creatinine ratio. (3) Results: The NGF/creatinine ratio was significantly higher in patients with pure OAB in comparison with other groups; however, it did not differ between the control group and the POP&OAB group. There was no correlation between NGF/creatinine ratio and age, menopausal status, BMI, parity or urodynamic findings. The NGF/creatinine ratio was not a prognostic factor for OAB symptoms’ resolution after surgical treatment of POP. (4) Conclusions: Urinary NGF excretion is not increased in women with OAB secondary to POP; thus, it may not serve as an OAB biomarker in these patients.

Üriner Sistem Semptomları Olan Multipl Sklerozlu Hastalarda Üriner Sinir Büyüme Faktörü Düzeyleri

Aim: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) in MS patients as markers of detrusor overactivity. &#x0D; Materials and Methods: 20 volunteers who were diagnosed with MS and who had urinary tract symptoms and 29 volunteers who were diagnosed with MS however who did not have urinary tract symptoms were included in the study. A comprehensive anamnesis and spot urine samples were obtained from the subjects. Twenty seven healthy volunteers with similar age and gender distribution were included for making a comparison with regard to NGF levels and spot urine samples were obtained.&#x0D; Results: Urinary NGF levels and NGF/urinary creatinine ratios were found lower in the group composed of MS patients who had urinary symptoms compared to the group composed of MS patients who did not have urinary symptoms but the difference was not statistically significant. These parameters were found lower in patient group who did not have urinary symptoms compared to control group however the difference was not statistically significant (p: 0,114 and 0,833)&#x0D; Conclusions: urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity.

Correlation between the NGF levels and questionnaire forms in patients receiving antimuscarinic treatment and those receiving onabotulinum toxin-A injection.

To compare nerve growth factor (NGF) levels in patients who received antimuscarinic, versus onabotulinum toxin-A (onaBoNT-A) injection, as well as to investigate whether there is a correlation between NGF levels, and 8-item overactive bladder questionnaire(OAB-V8), urogenital distress inventory (UDI)-6, and incontinence impact questionnaire (IIQ)-7 forms. Fourty adult patients with OAB were enrolled in this prospective study. An antimuscarinic was prescribed to 20 naive patients, and onaBoNT-A injection was administered to 20 patients, who were refractory to antimuscarinics. Urine samples were obtained before, and after 3rd and 6th months of treatment, and NGF levels were measured. Symptom scores of OAB-V8, UDI-6,and IIQ-7 were recorded. There was no significant difference between groups in terms of the initial OAB-V8, IIQ-7, and UDI-6 scores, whereas NGF values showed no significant difference over time in onaBoNT-A group (p=0.069, p=0.069). NGF levels were significantly lower in 3rd and 6th months, in patients receiving antimuscarinic (p=0.003, p=0.007); a strong correlation was found in 3rd month between the NGF levels, OAB-V8 scores (r=0.704, p=0.001), and IIQ-7 scores (r=0.676, p=0.001), and a moderate correlation between NGF levels, and UDI-6 scores (r=0.583, p=0.007). In the 6th months, a very strong correlation was found between NGF levels, and OAB-V8 scores (r=0.811, p=0.004), and a strong correlation was found between NGF levels, and IIQ-7 scores (r=0.671, p=0.001). In onaBoNT-A group, there was no significant correlation between NGF levels, and other variables. NGF level might be a good marker to evaluate effectiveness of treatment in patients receiving antimuscarinics, owing to correlation of urinary NGF levels with symptom scores. Lack of correlation in patients receiving onaBoNT-A injection could be a result of differences in the mechanism of action.

Genetic variants and expression changes in urgency urinary incontinence: A systematic review.

AimTo perform a systematic review summarizing the knowledge of genetic variants, gene, and protein expression changes in humans and animals associated with urgency urinary incontinence (UUI) and to provide an overview of the known molecular mechanisms related to UUI.MethodsA systematic search was performed on March 2, 2020, in PubMed, Embase, Web of Science, and the Cochrane library. Retrieved studies were screened for eligibility. The risk of bias was assessed using the ROBINS‐I (human) and SYRCLE (animal) tool. Data were presented in a structured manner and in the case of greater than five studies on a homogeneous outcome, a meta‐analysis was performed.ResultsAltogether, a total of 10,785 records were screened of which 37 studies met the inclusion criteria. Notably, 24/37 studies scored medium‐high to high on risk of bias, affecting the value of the included studies. The analysis of 70 unique genes and proteins and three genome‐wide association studies showed that specific signal transduction pathways and inflammation are associated with UUI. A meta‐analysis on the predictive value of urinary nerve growth factor (NGF) levels showed that increased urinary NGF levels correlate with UUI.ConclusionThe collective evidence showed the involvement of two molecular mechanisms (signal transduction and inflammation) and NGF in UUI, enhancing our understanding of the pathophysiology of UUI. Unfortunately, the risk of bias was medium‐high to high for most studies and the value of many observations remains unclear. Future studies should focus on elucidating how deficits in the two identified molecular mechanisms contribute to UUI and should avoid bias.

Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome.

Given the disputable link between nerve growth factor (NGF) and overactive bladder syndrome (OAB) and the lack of studies on its precursor (proNGF) in OAB, the aim of the study was to identify changes in the urinary levels of NGF and its proteolytic enzymes in aging women with OAB. We examined the urinary proNGF/NGF ratio and its processing enzymes in aging women (50-80years), comparing 20 controls and 20 subjects with OAB. In contrast to previous reports correlating NGF to OAB symptoms, we found that proNGF/NGF ratio in the OAB group was twice as high compared to controls (p = 0.009) with a lower NGF levels in women with OAB without statistical significance [1.36 (Q1, Q3: 0.668, 2.39) vs. 1.7 (Q1, Q3: 1.27, 3.045) pg/mg creatinine in control group, p = 0.05]. Enzymatic activity of MMP-7, the main enzyme for extracellular proNGF maturation, was significantly increased in the OAB group and correlated positively with scores of OAB symptoms questionnaires. However, this was counteracted by several-folds increase in the MMP-9 enzyme responsible for NGF proteolysis. While these findings highlight the importance of changes in the proteolytic enzymes to maintain proNGF/NGF balance in OAB, analysis of covariates showed that these changes were attributed to age, insulin resistance and renal function. NGF proteolysis imbalance can be clinically meaningful in OAB related to aging, rendering it as a potential therapeutic target. However, other age-related factors such as insulin resistance and renal function may contribute to the relationship between NGF and aging-related OAB phenotype.

Effect of Water Avoidance Stress on serum and urinary NGF levels in rats: diagnostic and therapeutic implications for BPS/IC patients

Nerve growth factor (NGF) is thought to play a key role in chronic pain felt by bladder pain syndrome/interstitial cystitis (BPS/IC) patients by activating its high affinity receptor tropomyosin-related kinase subtype A (Trk A). Whether this pathway is also involved in the aggravation of pain sensation during stress events was here investigated. The levels of plasmatic NGF were increased in rats submitted to Water Avoidance Stress test (WAS), compared to controls. The administration of the alpha1A adrenoceptors blocker silodosin prevented the increase of plasmatic NGF. Urinary NGF levels were also moderately increased in animals submitted to WAS. WAS increased pain behaviour score, lowered abdominal mechanical pain threshold and increase voiding bladder reflex activity. These changes were prevented by the administration of TrkA antagonist GW441756. These findings prompt the use of plasmatic NGF as diagnosis tool for chronic visceral painful conditions and opens therapeutic opportunities for TrkA receptors antagonist/NGF sequestration.

Nerve Growth Factor Levels are Associated with Overactive Bladder Symptoms and Long-Term Treatment Outcome after Transurethral Resection of the Prostate in Patients with Benign Prostatic Hyperplasia

We investigated changes in urinary nerve growth factor in patients with benign prostatic hyperplasia after transurethral prostate resection. We also assessed the association between nerve growth factor and changes of overactive bladder symptoms and long-term treatment outcomes after surgery. This was a prospective study of 178 patients at Peking University People's Hospital with benign prostatic hyperplasia between January 2011 and January 2013. Urinary nerve growth factor levels were determined preoperatively using a commercial enzyme-linked immunosorbent assay kit. We also determined prostate volume, I-PSS (International Prostate Symptom Score), quality of life, OABSS (Overactive Bladder Symptom Score), ultrasound estimated post-void residual urine and urodynamics before surgery. Urinary nervegrowth factor levels, I-PSS and OABSS were assessed again 1 year after transurethral prostate resection. Urinary nerve growth factor/creatinine levels differed between patients with moderate and severe lower urinary tract symptoms (mean ± SD 10.513 ± 4.255 vs 12.334 ± 4.048 pg/μmol, p = 0.002). There was no significant difference between patients with grades III/IV and V/VI bladder outlet obstruction (mean 11.285 ± 4.069 vs 11.781 ± 4.437 pg/μmol, p = 0.354). However, differences were significant for urinary nerve growth factor/creatinine levels in patients without overactive bladder, and mild, moderate and severe overactive bladder (mean 8.132 ± 3.489, 10.128 ± 3.817, 13.232 ± 3.290 and 14.029 ± 3.820 pg/μmol, respectively, p <0.001). One year after transurethral prostate resection we noted a decrease vs baseline in mean urinary nerve growth factor/creatinine (8.978 ± 4.022 pg/μmol, p <0.001), and I-PSS and OABSS (10.2 ± 5.4 and 4.3 ± 3.7, respectively, each p <0.001). Compared with the good outcome group, the fair/poor group had higher mean baseline urinary nerve growth factor/creatinine (12.319 ± 4.017 vs 11.015 ± 4.298 pg/μmol, p = 0.045), higher mean 1-year urinary nerve growth factor/creatinine (10.847 ± 4.267 vs 7.850 ± 3.419 pg/μmol, p <0.001) and a lesser mean postoperative change in urinary nerve growth factor/creatinine (1.472 ± 4.928 vs 3.165 ± 4.863 pg/μmol, p = 0.031). Nerve growth factor was associated with overactive bladder symptoms in patients with benign prostatic hyperplasia as well as with the assessment of successful long-term treatment outcome of bladder outlet obstruction with symptoms of overactive bladder.

Urinary Nerve Growth Factor as a Potential Biomarker of Treatment Outcomes in Overactive Bladder Patients.

PurposeThe aim of this study was to investigate urinary nerve growth factor (NGF) as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB) patients.MethodsWe enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr). Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker.ResultsUrinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62), but this was not significant (P=0.260). Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047). In those who did not experience recurrence (n=29), urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P<0.05).ConclusionsUrinary NGF is a potential biomarker for predicting the outcome of antimuscarinic treatment in OAB patients. This may provide useful information when deciding to stop antimuscarinic treatment in responders.

Urinary biomarkers in patients with detrusor underactivity with and without bladder function recovery.

Detrusor underactivity (DU) is frequently encountered in elderly patients. Part of patients with DU might have bladder function recovery after treatment. This study investigated urinary proteins in these DU patients with and without bladder function recovery. A total of 37 patients with chronic urinary retention and urodynamically proven DU were enrolled. After treatment, 24 DU patients had bladder function recovery whereas 13 had not, after 1-year follow-up. Urine collection at baseline was performed, and the urinary protein including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2) were measured by ELISA. Twenty urodynamically normal, 34 detrusor overactivity (DO) and 15 detrusor hyperactivity and inadequate contractility (DHIC) patients served as comparative groups. Urinary NGF levels were significantly higher than normal in patients with DU (9.2±20.3 vs 1.85±2.9pg/ml, p=0.037). Urinary BDNF level was only significantly higher in patients with DU than that of the control group (153±199 vs 77.4±47.7pg/ml, p=0.033) but not in patients with DHIC or DO. Compared with the control group, the urinary BDNF level was significantly higher in DU patients with bladder function recovery (190±239pg/ml, p=0.033) but not in patients without recovery (85.8±43.7pg/ml, p=0.612). The PGE2 level was significantly higher than the control group in DU patients with bladder function recovery (1290±836pg/ml, p<0.0001) but not in patients without recovery (383±237pg/ml, p=0.130). Patients with DU and higher urinary PGE2 and BDNF levels might have a chance to recover bladder function than those with a lower protein level.

Association of urinary nerve growth factor levels with erectile function in young men with type 2 diabetes mellitus.

We investigated urine nerve growth factor (NGF) levels and erectile dysfunction in diabetic men <45 years of age. Urinary NGF levels were measured in 72 diabetic men and 20 control subjects without lower urinary tract symptoms or erectile dysfunction. Participants were evaluated using the International Prostate Symptom Score, quality of life index, Overactive Bladder Symptom Score (OABSS), the five-item version of the International Index of Erectile Function questionnaire (IIEF-5), the patient perception of bladder condition questionnaire, measurement of flow rate and post-void residual urine volume. The results showed that the diabetic men had significantly higher urinary normalized NGF/creatinine (Cr) levels compared to the healthy controls (0.48±1.2 vs 0.01±0.01, P=0.04). The increased urinary NGF/Cr levels correlated negatively with the IIEF-5 total score (P=0.03, coefficient=-0.26, -0.02 to -0.47). The 42 patients with urinary NGF/Cr levels <0.05 had higher IIEF-5 scores than the 30 patients with urinary NGF/Cr level ⩾0.05 (20.2±4.6 vs 16.9±6.7, P=0.03). We conclude that urinary NGF levels were associated with erectile dysfunction in the men with type 2 <45 years of age.

Urinary Nerve Growth Factor Can Predict Therapeutic Efficacy in Children With Overactive Bladder

To assess urinary nerve growth factor (NGF) in children with overactive bladder (OAB) and to investigate the relationship between urinary NGF/creatinine (Cr) levels and OAB. Thirty-five children (27 boys and 8 girls) with OAB and 11 children (6 boys and 5 girls) without OAB or any other urinary symptoms, who served as controls, were included in this study. Urinary NGF levels were measured using enzyme-linked immunosorbent assay. The total urinary NGF levels were adjusted with the concentration of urinary creatinine (NGF/Cr level). Refractory OAB was defined as little improvement in OAB symptoms despite at least 3 months of urotherapy and anticholinergic agent treatment. Urinary NGF/Cr was compared between the children with OAB and the controls. The relationship between urinary NGF/Cr and treatment outcomes was also evaluated. Urinary NGF/Cr was significantly higher in the children with OAB when compared with those in the control group (0.65 ± 0.82 vs 0.11 ± 0.09, P = .0007). Improvement of OAB symptoms was observed in 26 out of 35 children (74%). The remaining 9 children showed refractory OAB symptoms (the refractory group). Urinary NGF/Cr was significantly higher in the refractory group than in the improved group (1.28 ± 1.34 vs 0.44 ± 0.39, P = .027). Urinary NGF/Cr was significantly higher in the children with OAB than in the controls, and was significantly higher in the refractory group than in the improved group. Urinary NGF/Cr could not only be a potential biomarker for children with OAB, but also a predictor of therapeutic efficacy in children with OAB.

Frequent nocturia episodes, a suboptimal response to treatment, and small bladder capacity predict the need for persistent antimuscarinic therapy or re-treatment after discontinuation of antimuscarinics in female overactive bladder.

The aim of the study was to investigate predictive factors of the need for persistent antimuscarinic therapy or re-treatment (PR) after discontinuation of antimuscarinic therapy for women with overactive bladder syndrome (OAB). All consecutive OAB women were enrolled in a prospective cohort study, and treated with solifenacin for 12 weeks in a University Hospital. Factors affecting PR were analyzed by Cox regression analysis. A total of 122 women were enrolled, and 107 women underwent 12-week solifenacin treatment. The dropout rate was 12.3%. The median follow-up period was 20.4 weeks (25-75 interquartile range: 16-102.3 wk). Twenty-seven (25%) women had PR. The median PR-free interval was 125.4 weeks (95% CI = 58.4 to - wk). Nocturia episodes (hazard ratio = 1.54), a suboptimal response (hazard ratio = 2.53), and the strong-desire volume (hazard ratio = 0.992) were independent predictors of PR by Cox backward stepwise regression analysis. The areas under the receiver-operating characteristic curves for nocturia episodes, a suboptimal response, and the strong-desire volume to predict PR were only 0.65, 0.63, and 0.59, respectively. In addition, normalized urinary nerve growth factor level was not significant (hazard ratio = 1.005, P = 0.68) for predicting PR. Furthermore, normalized urodynamic findings did not correlate with PR, a suboptimal response, or changes of Overactive Bladder Symptom Score and urinary nerve growth factor level. Frequent nocturia episodes, a suboptimal response, and small bladder capacity may predict PR after solifenacin treatment. These findings may serve as an initial guide in consultation regarding the treatment of OAB.

Urinary Neurotrophin Levels Increase in Women With Stress Urinary Incontinence After a Midurethral Sling Procedure

To investigate the association between urinary neurotrophin levels, maximum flow rate (Qmax) variation, and the appearance of urgency in women with stress urinary incontinence (SUI) after a midurethral sling (MUS) procedure. Thirty-one women with SUI were treated with a MUS. One year later, the outcome of surgery and the onset of urgency were assessed. At baseline and 1-year follow-up, urine was collected to measure nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentration, and Qmax variation was calculated. Urine samples from healthy women (n = 20) without lower urinary tract symptoms and overactive bladder (OAB) wet patients (n = 32) were used as controls. Urinary neurotrophin levels were measured by enzyme-linked immunosorbent assay and normalized to creatinine concentration. At baseline, urinary levels of NGF and BDNF were similar between SUI and healthy women (NGF: 2.10 ± 0.68 vs 1.99 ± 1.05; BDNF: 1.99 ± 0.71 vs 1.81 ± 0.90), and significantly inferior to OAB wet patients (NGF: 2.10 ± 0.68 vs 2.50 ± 0.54, P < .05; BDNF: 1.99 ± 0.71 vs 2.71 ± 0.45, P < .05). After surgery, there was a significant increase of both neurotrophins (vs baseline, P < .05) to the values of OAB wet patients. Moreover, there was a significantly higher percentage increase of NGF in women with de novo urgency than in those without lower urinary tract symptoms (P = .019). A trend for a higher mean Qmax reduction in women with de novo urgency was also found (P = .085). These findings suggest that increased bladder outlet resistance after a MUS may play a key role in the rise of urinary neurotrophins, promoting sensitization of bladder primary afferents and causing de novo urgency in susceptible patients.

Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome

Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine. Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay. Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls. Sensory hyperinnervation and basal urothelial p75NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress.

Can Urinary Nerve Growth Factor and Brain-Derived Neurotrophic Factor be used in the Diagnosis and Follow-Up of Voiding Dysfunction in Children?

We investigated the utility of urinary nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels as non-invasive markers for diagnosis and evaluation of treatment efficacy in children with overactive bladder (OAB). This prospective study included 24 children with OAB and 30 healthy controls. At the time of diagnosis, micturition disorder symptom scores (MDSS) were determined, blood and urine samples were collected, and anticholinergic therapy was initiated. Clinical responses were evaluated, at the third and sixth month of treatment, by MDSS and urinary NGF, BDNF, and creatinine levels. The patient group had significantly higher urine NGF/Cr ratio (975 &plusmn; 827 and 159 &plusmn; 84, respectively, P &lt; .001) and BDNF/Cr ratio (5.98 &plusmn; 5.78 and 0.81 &plusmn; 0.70, respectively, P &lt; .001) before treatment. Significantly decreased BDNF/Cr ratio was found at the sixth month (5.98 &plusmn; 5.78 and 2.24 &plusmn; 0.98, respectively, P = .004). NGF/Cr &gt; 360 was found to have 87.5% sensitivity and 100% specificity, and BDNF/Cr &gt; 1.288 was found to have 87.5% sensitivity and 83.3% specificity for OAB diagnosis. In conclusion, urine NGF/Cr and BDNF/Cr ratios may be useful markers for diagnosis of OAB. The BDNF/Cr ratio was found to be more significant in monitoring treatment response.&nbsp.