Yonsei Med J.  2015 Jan;56(1):204-211. 10.3349/ymj.2015.56.1.204.

NGF and HB-EGF: Potential Biomarkers that Reflect the Effects of Fesoterodine in Patients with Overactive Bladder Syndrome

• Kim SR
• Moon YJ
• Kim SK
• Bai SW

• KMID: 2352808
• DOI: http://doi.org/10.3349/ymj.2015.56.1.204

Abstract

PURPOSE
To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms.
MATERIALS AND METHODS
This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks.
RESULTS
Urinary levels of NGF/Cr (OAB: 1.13+/-0.9 pg/mg; control: 0.5+/-0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73+/-6.55 pg/mg; control: 4.45+/-2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13+/-0.08 pg/mg; 16 weeks: 0.60+/-0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73+/-6.55 pg/mg; 16 weeks: 4.72+/-2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores.
CONCLUSION
Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.

Keyword

Heparin-binding EGF-like growth factor; nerve growth factor; overactive bladder; questionnaire; urinary biomarkers

MeSH Terms

Adult
Benzhydryl Compounds/pharmacology/*therapeutic use
Biological Markers/urine
Case-Control Studies
Creatinine/urine
Female
Heparin-binding EGF-like Growth Factor/*urine
Humans
Male
Middle Aged
Nerve Growth Factor/*urine
Questionnaires
Treatment Outcome
Urinary Bladder, Overactive/*drug therapy/physiopathology/*urine
Urodynamics
Benzhydryl Compounds
Biological Markers
Creatinine
Heparin-binding EGF-like Growth Factor
Nerve Growth Factor

Figure

• 

  Fig. 1 Changes in the urinary levels of nerve growth factor/creatinine (NGF/Cr) and heparin-binding epidermal growth factor-like growth factor/creatinine (HB-EGF/Cr) in patients with overactive bladder (OAB) syndrome at baseline and 1 and 4 months after treatment and in the control patients at baseline and 1 month after surgery (mean±SD). A post hoc analysis was used to test statistical significance (A), (B) urinary NGF/Cr and HB-EGF/Cr levels in OAB patients. Group 1: OAB patients, Group 2: controls. *p<0.05.

• 

  Fig. 2 Symptomatic changes in patients with overactive bladder (OAB) syndrome are shown at baseline and after 4 months of fesoterodine treatment. (A) Mean Overactive Bladder symptomatic score (OABSS) with standard deviation (SD) for the four questions. (B) Mean Overactive Bladder Questionnaire (OAB q) scores with SD for total health-related quality of life (HRQL), the four HRQL domains, and symptom bother. A positive score change in total HRQL and its domains indicates improvement; a negative score change in symptom bother indicates improvement (*p<0.001 vs. baseline).

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