title: Urinary Biomarkers in Women with Refractory Urgency Urinary Incontinence Randomized to Sacral Neuromodulation versus OnabotulinumtoxinA Compared to Controls.
abstract: We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes.
  
  
  
  First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ≤0.01 and p ≤0.004 represented moderate evidence of an association with outcomes.
  
  
  
  Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother.
  
  
  
  Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: hrichter@uabmc.edu.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Richter
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Pamela
authors.initials: P
authors.lastname: Moalli
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Amundsen
authors.affiliation: University of Colorado, Denver, Colorado.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
authors.affiliation: RTI International, Research Triangle Park, North Carolina.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wallace
authors.affiliation: University of New Mexico, Albuquerque, New Mexico.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rogers
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Deborah
authors.initials: D
authors.lastname: Myers
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Maria
authors.initials: M
authors.lastname: Paraiso
authors.affiliation: University of California-San Diego, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Albo
authors.affiliation: University of Texas Southwestern, Dallas, Texas.
authors.forename: Haolin
authors.initials: H
authors.lastname: Shi
authors.affiliation: RTI International, Research Triangle Park, North Carolina.
authors.forename: Tracy
authors.initials: T
authors.lastname: Nolen
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Baltimore, Maryland.
authors.forename: Susie
authors.initials: S
authors.lastname: Meikle
authors.affiliation: University of Texas Southwestern, Dallas, Texas.
authors.forename: R Ann
authors.initials: RA
authors.lastname: Word
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008160:Lumbosacral Plexus; D008875:Middle Aged; D011446:Prospective Studies; D004561:Transcutaneous Electric Nerve Stimulation; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000628:therapy* / Q000652:urine*; D053202:Urinary Incontinence, Urge / Q000188:drug therapy / Q000628:therapy* / Q000652:urine*
chemical_list: D015415:Biomarkers; D019274:Botulinum Toxins, Type A; C000629279:onabotulinum toxin A
keywords: biomarkers; neuropeptides; onabotulinumtoxinA; urgency; urinary bladder; urinary incontinence