title: Urinary neurotrophic factors in healthy individuals and patients with overactive bladder.
abstract: OBJECTIVE
  We investigated urinary levels of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in healthy individuals and patients with overactive bladder.
  
  
  METHODS
  Urine from 40 healthy volunteers, half of them male and half female, was collected in the morning, afternoon and evening on 2 occasions 3 months apart. Morning urine samples were collected from 37 female naïve patients with overactive bladder. A total of 24 patients were followed. Urine was collected after a 3-month lifestyle intervention and after 3-month antimuscarinic treatment (oxybutynin 10 mg, extended release). Urinary nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor concentrations were measured by enzyme-linked immunosorbent assay and normalized to creatinine. Patients completed a 7-day bladder diary combined with an urgency severity scale. The number of urgency episodes per week was counted.
  
  
  RESULTS
  In healthy individuals urinary levels of neurotrophic factors were stable. In patients with overactive bladder the nerve growth factor-to-creatinine (mean ± SD 488.5 ± 591.8 vs 188.3 ± 290.2, p = 0.005) and brain-derived neurotrophic factor-to-creatinine (mean 628.1 ± 590.5 vs 110.4 ± 159.5, p <0.001) ratios were significantly higher than in healthy women. No significant differences were found in the glial cell line-derived neurotrophic factor-to-creatinine ratio. After lifestyle intervention the nerve growth factor-to-creatinine and brain-derived neurotrophic factor-to-creatinine ratios decreased to a mean of 319.7 ± 332.3 and 432.5 ± 589.0 (vs baseline p = 0.318 and 0.033, respectively). After antimuscarinic treatment the nerve growth factor-to-creatinine and brain-derived neurotrophic factor-to-creatinine ratios further decreased to a mean of 179.8 ± 237.9 and 146.6 ± 264.9 (vs baseline p = 0.008 and <0.001, respectively). There was no significant variation in the glial cell line-derived neurotrophic factor-to-creatinine ratio at any time point. The reduction in the number of urgency episodes per week correlated with the brain-derived neurotrophic factor-to-creatinine variation (Pearson product-moment correlation coefficient r = 0.607, p = 0.006) but not with the nerve growth factor-to-creatinine ratio (r = 0.396, p = 0.094).
  
  
  CONCLUSIONS
  The urinary nerve growth factor-to-creatinine and brain-derived neurotrophic factor-to-creatinine ratios are increased in patients with overactive bladder. These findings may have pathophysiological and clinical implications.
authors.affiliation: Department of Urology, Hospital de S. João, University of Porto, Porto, Portugal. tiagoantuneslopes@gmail.com
authors.forename: Tiago
authors.initials: T
authors.lastname: Antunes-Lopes
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Barros
authors.forename: Francisco
authors.initials: F
authors.lastname: Botelho
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Silva
authors.forename: Célia D
authors.initials: CD
authors.lastname: Cruz
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruz
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000652:urine*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000652:urine*; D012016:Reference Values; D053201:Urinary Bladder, Overactive / Q000652:urine*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020932:Nerve Growth Factor