Microbial-Derived Uremic Toxins as a Factor of Vascular Remodeling in Patients Receiving Hemodialysis Treatment

Abstract

BACKGROUND: In the population of patients with chronic kidney disease, higher levels of microbial-derived uremic toxins, regardless of the presence of traditional risk factors, predict an increased risk of adverse outcomes due to various cardiovascular complications. Meanwhile, the mechanisms of this association remain largely unexplored.

AIM: To study associations between concentrations of microbial-derived uremic toxins indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide and vascular remodeling in patients receiving hemodialysis treatment.

METHODS: This study included 80 hemodialysis patients and 80 individuals with normal kidney function. The groups were comparable by gender, age, body mass index and smoking intake status. The presence and severity of vascular remodeling were assessed using cardio-ankle vascular index, carotid intima-media thickness, abdominal aortic calcification scores and brachial artery endothelium-dependent vasodilation (flow-mediated dilation). The concentrations of indoxyl sulfate and p-cresyl sulfate in blood serum were determined by ELISA. The serum levels of trimethylamine-N-oxide were assessed by liquid chromatography/mass spectrometry.

RESULTS: Compared with healthy controls, dialysis patients showed significantly higher cardio-ankle vascular index (9.5 ± 1.5 vs. 7.8 ± 1.2, p < 0.001) and carotid intima-media thickness (1.04 ± 0.2 vs. 0.95 ± 0.15 mm, p = 0.001), as well as lower flow-mediated dilation (3.9 ± 1.2 vs. 7.5 ± 0.8%, p < 0.001). The median abdominal aortic calcification in this group was 4.5 (0–9.0). In the multivariate regression analysis adjusted for other dependent factors, indoxyl sulfate was found to be an independent determinant of cardio-ankle vascular index (β = 0.266; p = 0.002) and carotid intima-media thickness (β = 0.372; p = 0.001). Similarly, p-cresyl sulfate was a predictor of cardio-ankle vascular index (β = 0.143; p = 0.048) and abdominal aortic calcification (β = 0.21; p = 0.032), while trimethylamine-N-oxide was independently associated with cardio-ankle vascular index (β = 0.223; p = 0.004), carotid intima-media thickness (β = 0.208; p = 0.024) and flow-mediated dilation (β = −0.262; p = 0.004).

CONCLUSION: The relationship between an increased serum microbial-derived uremic toxins and surrogate markers of cardiovascular diseases (cardio-ankle vascular index, carotid intima-media thickness, abdominal aortic calcification and flow-mediated dilation) found in this study may indicate a significant role of indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide in vascular remodeling in individuals receiving hemodialysis treatment.

Keywords

microbial-derived uremic toxins / indoxyl sulfate / p-cresyl sulfate / trimethylamine-N-oxide / vascular remodeling / cardio-ankle vascular index / carotid intima-media thickness / abdominal aortic calcification / flow-mediated dilation / chronic kidney disease / end stage renal disease / hemodialysis

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