Nerve Growth Factor Levels are Increased in Urine but Not Urothelium in Patients With Detrusor Overactivity

Urinary nerve growth factor (NGF) has gained great interest in detecting detrusor overactivity (DO) in patients with overactive bladder syndrome. However, the source of urinary NGF has not been fully elucidated. We investigated the relationship of urinary NGF levels and NGF expression in the urothelium and suburothelium of patients with idiopathic DO. Bladder tissues not involving the muscle layer were obtained from 18 patients with urodynamic DO with or without bladder outlet obstruction. Urine samples at full bladder were also collected for urinary NGF measurement. Fourteen bladder and urine samples obtained from patients with stress urinary incontinence but no lower urinary tract symptoms served as controls. Urinary NGF levels were measured by ELISA. Expression of NGF in the urothelium was measured by immunohistochemical staining using anti-human antibody, and stained sections were captured by a digital image system. Correlation analysis between the urothelial NGF levels in the bladder tissue and urinary NGF/creatinine (Cr) were performed. Urinary NGF/Cr levels were significantly higher in DO patients (0.78 ± 1.26) compared with the control group (0.01 ± 0.02; p= 0.02). However, NGF expression in the DO urothelium (125.87 ± 21.79) were not significantly higher than the controls (135.60 ± 13.50; p = 0.142). Correlation between urinary and urothelial NGF levels were not significant in both controls and patients with DO (Spearman's r = −0.32, p = 0.26 and Spearman's r = 0.28, p = 0.22, respectively). DO patients have higher urinary NGF/Cr levels than controls. However, urothelial NGF expression was no different between the two groups. The results suggest elevated urinary NGF levels in DO patients might not be due to urothelial NGF overproduction.