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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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 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.