Dr. Campeau began by explaining that obesity and insulin resistance are strongly associated with lower urinary tract symptoms, and particularly with OAB. The metabolic syndrome is characterized by low HDL cholesterol, visceral obesity, insulin resistance, hypertension, and high trigylcerides. This puts the patient in a pro-inflammatory state of pelvic ischemia, oxidative stress, and sympathetic overactivity. Her research is focused specifically on elements of the citric acid cycle, of which the metabolic products are expressed at a higher level in conditions of metabolic stress.
A recent study of Dr. Campeau’s looked OAB urinary metabolic markers. She evaluated 40 women, ages 50-80, without diabetes, liver or kidney disease. 20 of the women had OAB and the other 20 served as controls. A metabolomic urinary analysis was performed and found 3 urinary metabolites that were predictive of OAB symptoms (fumaric, malic, and hydroxyisobutyric), and 4 which were correlated with symptom severity (fumaric, malic, pyroglutamic, and hydroxyisobutyric).
A particular area of interest for Dr. Campeau is succinate, a product of the citric acid cycle which increases in states of metabolic stress. Succinate binds to GPR91 receptor which is present on urothelial and smooth muscle cells. Succinate binding leads to intracellular signaling, which ultimately leads to decreased bladder compliance, capacity, and contractility. Succinate leads to down regulation of the beta 3 adrenergic receptor, and increased levels of succinate cause impaired mirabegron and beta 3-receptor interaction.
Dr. Campeau concluded that OAB patients have a higher urinary levels of citiric acid cycle intermediates, and that succinate and the citric acid cycle are potential targets for treatment of OAB. Her ultimate vision was to develop personalized medicine which is based on the metabolic profile and urinary metabolome of individual patients. This was a fascinating presentation that may represent the future of urologic treatment of OAB.
Presented by: Lysanne Campeau, MD
Written by: Dena Moskowitz, MD, Fellow, Female Pelvic Medicine and Reconstructive Surgery, Virginia Mason Medical Center, Twitter: @demoskowitz at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA