INTRODUCTION AND OBJECTIVE:
Overactive Bladder (OAB) is diagnosed based on symptoms and often treated based on patient preference. A urine biomarker could phenotype refractory OAB and identify those who would benefit from chemodenervation vs neuromodulation. Metabolomics is the analysis of metabolic profiles. Urine metabolites may be potential biomarkers for OAB yet little is known about the effect of third line treatments like bladder onabotulinumtoxin-A (BTX-A) on the urinary metabolome. Our study objective was to evaluate changes in the urinary metabolome and correlate with OAB-V8 symptom score change after BTX-A injections in women with refractory OAB.
Women over 18 years with non-neurogenic refractory OAB were recruited from our female urology clinic. OAB-V8 questionnaires and urine samples were collected before and after 100 units BTX-A injection. Samples were aliquoted, frozen on dry ice, and stored in a -80ºC freezer. Urine metabolomic analysis was conducted by Human Metabolome Technology Inc., Tsuruoka, Japan, and data was expressed as percent change from pre-treatment values. These were correlated with improvement in OAB-V8 Scores categorized as: no improvement (<8), mild improvement (8-16), marked improvement (>17). Change in metabolite levels was compared between groups using ANOVA, and correlations between metabolites and OAB-V8 scores evaluated using linear regression.
Fifty-four urine samples were collected from 21 women. Mean age was 56 (46-56). 3 patients had diabetes, 10 had chronic pain disorders, 8 had prior pelvic surgery. Of 42 metabolites, Quinic Acid (p=0.01), N-o-Toluoyl-glycine-1-Phenaceturic acid-1 (p=0.02) and Adenosine (p=0.01) levels were significantly lower and N8-Acetylspermidine (p=0.01) levels significantly higher in the marked improvement vs. no improvement group. In linear regression models, N8-acetylspermidine (p=0.02) and Quinic Acid levels (p=0.009) significantly correlated with improvement in OABV-8 scores, Figure 1.
Bladder BTX-A injection changes the urinary metabolome, with corresponding OAB score improvement. Further investigation of urine metabolites could provide objective data and biomarkers to follow OAB treatment response, and ultimately identify a subset of women who would benefit from certain third line therapies.
Source of Funding: