Urinary Neurotrophic Factors in Healthy Individuals and Patients with Overactive Bladder

Purpose: 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. Materials and 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 naive 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.