title: Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection.
abstract: BACKGROUND
  Increased nerve growth factor (NGF) levels have been reported in the bladder tissue and urine of patients with overactive bladder and detrusor overactivity (DO). Determination of urinary NGF level could serve as a valuable biomarker for the diagnosis and monitoring of disease progression of DO.
  
  
  OBJECTIVE
  To investigate NGF levels in patients with DO and after treatment including detrusor botulinum toxin A (BoNT-A) injections.
  
  
  METHODS
  A cross-sectional study was performed in a referred center. Participants included 143 patients with idiopathic DO (IDO) and 100 with neurogenic DO (NDO) who were untreated, well-treated, and failed-treated with antimuscarinics. Thirty-eight subjects without lower urinary tract symptoms served as controls. Detrusor injection of BoNT-A (100 U for IDO, 200 U for NDO) was given to 24 patients with IDO and 19 with NDO who had failed antimuscarinic treatment.
  
  
  METHODS
  Urine samples were obtained from controls and patients. Urinary NGF levels were measured by ELISA and normalized by urine creatinine level (NGF/Cr). The urinary NGF/Cr levels in controls and patients with DO at baseline and 3 mo after BoNT-A injection were compared.
  
  
  CONCLUSIONS
  The mean urinary NGF/Cr levels were significantly higher in 66 patients with untreated IDO (mean+/-standard deviation, 1.44+/-2.66, p=0.000) and 59 with untreated NDO (0.62+/-1.22, p=0.000) compared to controls (0.005+/-0.019). Patients with well-treated IDO or NDO had reduced NGF/Cr levels, whereas those with failed-treated IDO or NDO did not. Patients who responded to BoNT-A treatment had significantly reduced urinary NGF/Cr levels in both the IDO (0.07+/-0.12, p=0.025) and NDO (0.096+/-0.17, p=0.033) groups compared to baseline levels. However, the NGF levels remained significantly higher at 3 mo in 7 IDO (1.01+/-1.25) and 5 NDO (1.64+/-2.39) patients who failed BoNT-A treatment. The major limitation of this study is the wide deviation of the urinary NGF levels and lack of age controls.
  
  
  CONCLUSIONS
  Urinary NGF level is a sensitive biomarker for the diagnosis of IDO and NDO and can be used as a tool to evaluate the therapeutic effect of detrusor BoNT-A injection.
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Liu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Hann-Chorng
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000652:urine*; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009465:Neuromuscular Agents; D020932:Nerve Growth Factor; D019274:Botulinum Toxins, Type A