Hsin-Tzu Liu

Urinary Nerve Growth Factor Levels are Elevated in Patients with Detrusor Overactivity and Decreased in Responders to Detrusor Botulinum Toxin-A Injection

BACKGROUND Increased nerve growth factor (NGF) levels have been reported in the bladder tissue and urine of patients with overactive bladder and detrusor overactivity (DO). Determination of urinary NGF level could serve as a valuable biomarker for the diagnosis and monitoring of disease progression of DO. OBJECTIVE To investigate NGF levels in patients with DO and after treatment including detrusor botulinum toxin A (BoNT-A) injections. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study was performed in a referred center. Participants included 143 patients with idiopathic DO (IDO) and 100 with neurogenic DO (NDO) who were untreated, well-treated, and failed-treated with antimuscarinics. Thirty-eight subjects without lower urinary tract symptoms served as controls. Detrusor injection of BoNT-A (100 U for IDO, 200 U for NDO) was given to 24 patients with IDO and 19 with NDO who had failed antimuscarinic treatment. MEASUREMENTS Urine samples were obtained from controls and patients. Urinary NGF levels were measured by ELISA and normalized by urine creatinine level (NGF/Cr). The urinary NGF/Cr levels in controls and patients with DO at baseline and 3 mo after BoNT-A injection were compared. RESULTS AND LIMITATIONS The mean urinary NGF/Cr levels were significantly higher in 66 patients with untreated IDO (mean+/-standard deviation, 1.44+/-2.66, p=0.000) and 59 with untreated NDO (0.62+/-1.22, p=0.000) compared to controls (0.005+/-0.019). Patients with well-treated IDO or NDO had reduced NGF/Cr levels, whereas those with failed-treated IDO or NDO did not. Patients who responded to BoNT-A treatment had significantly reduced urinary NGF/Cr levels in both the IDO (0.07+/-0.12, p=0.025) and NDO (0.096+/-0.17, p=0.033) groups compared to baseline levels. However, the NGF levels remained significantly higher at 3 mo in 7 IDO (1.01+/-1.25) and 5 NDO (1.64+/-2.39) patients who failed BoNT-A treatment. The major limitation of this study is the wide deviation of the urinary NGF levels and lack of age controls. CONCLUSIONS Urinary NGF level is a sensitive biomarker for the diagnosis of IDO and NDO and can be used as a tool to evaluate the therapeutic effect of detrusor BoNT-A injection.

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

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.

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

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

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

Pilot Study of Liposome-encapsulated OnabotulinumtoxinA for Patients with Overactive Bladder: A Single-center Study

BACKGROUND Intradetrusor onabotulinumtoxinA (BoNT-A) injection benefits overactive bladder (OAB) patients, but increased postvoid residual (PVR) urine volume and urinary tract infection (UTI) remain risks. Intravesical instillation of liposomal BoNT-A instead of injection could prevent such adverse events. OBJECTIVE To evaluate instillation of liquid liposomal BoNT-A (Lipotoxin) for the treatment of OAB and to determine its mechanism of action. DESIGN, SETTING, AND PARTICIPANTS A double-blind randomized parallel controlled pilot trial in 24 OAB patients at a single tertiary center. INTERVENTION Patients were randomly assigned to intravesical instillation of Lipotoxin containing 80 mg liposomes and 200 U BoNT-A or normal saline (N/S). Patients were retreated with Lipotoxin 1 mo later if they failed the first treatment. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS Voiding diaries, OAB symptom scores, urodynamic studies, and adverse events were monitored. The primary end point was change of total urinary frequency per 3 d at 1 mo after treatment. Immunohistochemistry and Western blotting for synaptic vesicle glycoprotein 2A (SV2A) and synaptosomal-associated protein, 25 kDa (SNAP25) were performed at baseline and 3 mo after treatment. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. RESULTS AND LIMITATIONS At 1 mo after treatment, the change of urinary frequency per 3 d significantly improved in the Lipotoxin group (n=12; median: -6.50; interquartile range [IQR]: -18.3 to -0.25; p=0.008) but not in the N/S group. (n=12.0; IQR: -7.75 to 8.0; p=0.792). Urgency episodes also showed a significant decrease in the Lipotoxin group (-12.0; IQR: -20.3 to -2.75; p=0.012) but not in the N/S group (-1.0; IQR: -11.0 to 2.5; p=0.196). SV2A and SNAP25 were expressed in urothelial cells and suburothelial tissues. However, the protein expression did not significantly differ between responders and nonresponders at 3 mo after treatment. CONCLUSIONS Intravesical Lipotoxin instillation effectively reduced frequency episodes 1 mo after treatment in OAB patients without any increase in PVR or risk of UTI. PATIENT SUMMARY We demonstrated that intravesical Lipotoxin instillation reduced frequency episodes at 1 mo in overactive bladder patients. This procedure is safe, without an increase in postvoid residual or the risk of urinary tract infection.

Urinary nerve growth factor in women with overactive bladder syndrome.

Study Type – Aetiology (case series)

Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome.

A single set of botulinum toxin A (BoNT‐A) injections relieves clinical symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks long‐term effect. An inadequate anti‐inflammatory effect is likely to cause treatment failure. The study shows that chronic inflammation and apoptotic signalling molecules are significantly reduced after repeated intravesical BoNT‐A injection in patients with IC/BPS. It also shows that repeated BoNT‐A injections are necessary to achieve greater success in the treatment of IC/BPS.

Increased expression of transient receptor potential vanilloid subfamily 1 in the bladder predicts the response to intravesical instillations of resiniferatoxin in patients with refractory idiopathic detrusor overactivity

To investigate the correlation of transient receptor potential vanilloid subfamily 1 (TRPV1) mRNA expression levels and the clinical outcome of intravesical resiniferatoxin treatment in patients with idiopathic detrusor overactivity (IDO), as such treatment with vanilloids can be effective for DO.

Urinary nerve growth factor level is correlated with the severity of neurological impairment in patients with cerebrovascular accident

To measure urinary nerve growth factor (uNGF, essential in nerve growth and regeneration) levels in patients with a cerebrovascular accident (CVA), to determine whether uNGF could be a biomarker for predicting the neurological deficits in CVA, as the level of uNGF increases in patients with idiopathic detrusor overactivity (DO) and incontinence.

Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms

Objectives: To measure urinary nerve growth factor (NGF) levels in patients with several urinary tract diseases under different conditions and compare with NGF levels in patients with overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS).