Background: Arterial stiffness (AS), an important determinant of systolic hypertension, is associated with an increased cardiovascular risk. AS is higher in chronic kidney disease, particularly among patients undergoing hemodialysis (HD). In HD patients, alterations in the gut microbiota contribute to dysregulation of bile acid (BA) metabolism. Certain BAs, through activation of the Farnesoid X Receptor (FXR), can accelerate vascular calcification and, consequently, increase AS. Our study aims to explore the potential association between BA metabolites and AS in patients undergoing HD.
METHODS AND RESULTS: Methodes: This cross-sectional study examined the relationship between BA metabolites and AS in 208 HD patients (61% male; mean age 67 ± 15). AS was assessed by pulse wave velocity (PWV), with carotid-femoral PWV (CF-PWV) measuring large artery stiffness and carotid-radial PWV (CR-PWV) assessing medium-sized artery stiffness. The complete BA profile included total, glucuronidated, unconjugated, conjugated, taurine-conjugated, glycine-conjugated, primary, and secondary BAs by mass spectroscopy. Resultes: Bile acid profiling revealed that tauro-conjugated bile acids were significantly elevated in male patients, while overall total bile acid concentrations were similar between sexes. Importantly, glucuronide-conjugated bile acids were strongly correlated with CF-PWV, a major indicator of large artery stiffness. Furthermore, the ratio of carotid-femoral to carotid-radial PWV (CF/CR-PWV) showed a positive association with total bile acids and glucuronide-conjugated bile acids. Multivariate regression analyses, adjusted for diabetes and diastolic blood pressure, confirmed that in male patients, large artery stiffness increased in association with higher levels of glucuronide-conjugated bile acids and a higher glucuronide-to-total bile acid ratio. In contrast, among female patients, the aortic–brachial PWV ratio increased with glucuronide-conjugated bile acids, but large artery stiffness itself was not significantly impacted by these metabolites.
Conclusion: Glucuronide BAs were strongly correlated with CF PWV, a key marker of AS, highlighting their potential role in vascular dysfunction in this population. These findings suggest that altered BA metabolism, particularly glucuronidation, may contribute to AS and could serve as a potential target for understanding and mitigating cardiovascular risks in HD patients.
