To measure urinary biomarker levels in women with refractory urgency urinary incontinence (UUI) and controls at baseline and 6 months post treatment from sacral neuromodulation (SNM) or intradetrusor injection onabotulinumtoxinA and to assess association of baseline biomarkers to post treatment UUI episodes (UUIE) and overactive bladder (OAB) symptom bother outcomes.
First morning urines were collected from consented trial participants and age-matched women without UUI. Biomarkers reflecting general inflammation, neuro-inflammation, afferent neurotransmitters, and tissue remodeling were measured using standardized ELISA and activity assays as appropriate. Symptom bother was assessed by Overactive Bladder (OAB) Questionnaire and UUI episodes by bladder diary. Linear models were used to examine differences in mean biomarker levels, and change in UUIE and symptom bother between baseline and six months. A p-value ≤0.01 represented modest evidence of a potential association and ≤0.004 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 (NTx, p<0.001). Changes in biomarker levels 6 months post intervention included decreases in collagenase (p<0.001) in both treatment groups andincreases in interleukin-8 (p=0.002) and matrix metalloprotease-9 (p<0.001) in the onabotulinumtoxinA group. Higher baseline CGRP across both treatments (p=0.007) and nerve growth factor in the onabotulinumtoxinA arm (p=0.007) were associated with less reduction in OAB symptom bother.
Refractory UUI is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiologic mechanisms and response to treatment.
The Journal of urology. 2017 Jan 13 [Epub ahead of print]
Holly E Richter, Pamela Moalli, Cindy L Amundsen, Anna P Malykhina, Dennis Wallace, Rebecca Rogers, Deborah Myers, Maria Paraiso, Michael Albo, Haolin Shi, Tracy Nolen, Susie Meikle, R Ann Word, Pelvic Floor Disorders Network
University of Alabama at Birmingham, Birmingham, AL. Electronic address: ., University of Pittsburgh, Pittsburgh, PA. Electronic address: ., Duke University, Durham, NC. Electronic address: ., University of Colorado, Denver, Colorado. Electronic address: ., RTI, Research Triangle Park, NC. Electronic address: ., University of New Mexico, Albuquerque, NM. Electronic address: ., Brown University, Providence, RI. Electronic address: ., Cleveland Clinic, Cleveland, Ohio. Electronic address: ., University of California, San Diego, San Diego, CA. Electronic address: ., University of Texas, Southwestern, Dallas, TX. Electronic address: ., RTI, Research Triangle Park, NC. Electronic address: ., Eunice Kennedy Shriver National Institute of Child Health and Human Development, Baltimore, MD. Electronic address: ., University of Texas, Southwestern, Dallas, TX. Electronic address: .