The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis

Abstract

Objective: p-Cresyl sulfate (PCS) and indoxyl sulfate (IS) have been reported to predict poor clinical outcomes in hemodialysis (HD) patients. However, little is known about the effect of the two toxins on peripheral arterial disease (PAD) and vascular access dysfunction. Our objective was to explore the association between the two toxins and PAD and vascular access failure (VAF) in a hemodialysis-based cohort.

Methods: We enrolled 100 stable and eligible HD patients from a single medical center. These patients were screened for PAD by machine and recorded as ABI (ankle brachial index) and brachial-ankle PWV (pulse wave velocity). Serum levels of PCS, IS and biochemical data were also collected concurrently. In addition, we also recorded the first event of VAF and frequency of PTA and thrombectomy during 3-year follow-up.

Results: Total and free PCS were correlated to right and left ABI and PWV (p < 0.01), and total IS was associated with right and left ABI (p < 0.01) by Pearson's analysis. Repeated measuring by mixed model analysis revealed that serum albumin (p = 0.003), cholesterol (p = 0.01) and total PCS (p = 0.031) had significant correlation with ABI after adjusting other confounding factors. As for brachial-ankle PWV, serum triglyceride (p = 0.002), total IS (p = 0.04) and total PCS (p = 0.050) reached significance finally. In addition, multivariate Cox regression analysis revealed dialysis length and total PCS were related to AV-shunt failure event (Hazard Ratio: 1.14, p = 0.01, and Hazard Ratio: 1.04, p = 0.04, respectively). Both of total and free PCS and IS were also positively linked to numbers of PTA and thrombectomy. Further, the Kaplan-Meier analysis showed only total PCS was significantly associated with vascular access failure event (log rank P = 0.02).

Conclusion: This study shows that the serum levels of PCS and IS were associated with PAD and total PCS could be a valuable determinant of access viability other than traditional or nontraditional risk factors in HD patients.