Serum Phenylacetylglutamine Is a Potential Risk Factor for Aortic Stiffness in Patients with Chronic Hemodialysis

Background/Objectives: Phenylacetylglutamine (PAG), a gut microbiota-derived metabolite, may contribute to the development of cardiometabolic diseases. The diagnostic value of PAG for vascular dysfunction in hemodialysis (HD) remains unclear. This study assessed how serum PAG levels relate to carotid-femoral pulse wave velocity (cfPWV), which is a validated index of aortic stiffness, in patients on maintenance HD. Methods: A total of 138 patients on maintenance HD were enrolled. Participants with cfPWV values greater than 10 m/s were categorized as having aortic stiffness. Serum PAG levels were measured using high-performance liquid chromatography-mass spectrometry. Results: Aortic stiffness was present in 33.3% of patients. Those with aortic stiffness were older (p = 0.016), had a higher prevalence of diabetes mellitus (p = 0.030) and hypertension (p < 0.001), and had higher systolic (p < 0.001) and diastolic (p < 0.001) blood pressures, glucose (p = 0.005), and serum PAG (p < 0.001) levels. Multivariable analysis identified serum PAG (odds ratio [OR] = 1.903; 95% confidence interval [CI] = 1.171-3.094, p = 0.009) and age (OR = 1.042, 95% CI = 1.001-1.084, p = 0.044) as independent determinants of aortic stiffness. Linear regression revealed that PAG (p < 0.001), systolic blood pressure (p < 0.001), age (p = 0.013), and glucose level (p = 0.024) were positively associated with cfPWV. Conclusions: Among individuals undergoing maintenance HD, higher serum PAG levels independently predicted greater aortic stiffness. PAG may be a potential diagnostic biomarker for vascular stiffness and a tool for cardiovascular risk stratification in this population.