Urinary metabolomics predict the severity of overactive bladder syndrome in an aging female population.

Abstract

To identify urinary metabolites that can facilitate the diagnosis and the characterization of the underlying pathophysiology of the association between the overactive bladder syndrome (OAB) and metabolic syndrome. We used gas chromatography-mass spectrometry to compare the urinary metabolome of 20 females of 50-80years of age with OAB to that of 20 controls of the same age group. We performed urinary metabolomic analysis and obtained serum markers of metabolic syndrome for each subject. Participants completed a clinical evaluation and validated self-reported questionnaires of lower urinary tract symptoms as well as a one-day voiding diary. In the OAB subjects, we identified increased urinary levels of markers of mitochondrial dysfunction (itaconate, malate and fumarate), oxidative stress (L-pyroglutamate and α-hydroxyglutarate) and ketosis (α-hydroxybutyrate and α-hydroxyisobutyrate). The increased levels of these markers correlated significantly with the OAB symptoms score on questionnaires. We found, using a multiple linear regression model, that age, blood glucose and urine metabolites (malate, fumarate and α-hydroxyisobutyrate) were significant predictive factors of OAB severity. Fumarate had high sensitivity as a biomarker of OAB due to metabolic syndrome, based on a statistically significant receiver-operating characteristic (ROC) curve, indicating its potential as a diagnostic tool. Altogether, these findings establish that urinary metabolites of mitochondrial dysfunction, ketosis and oxidative stress can be potential biomarkers of OAB severity and diagnosis.