**1. Introduction**

Arterial sti ffness (AS), which is a risk factor for cardiovascular (CV) disease (CVD), has long been recognized as the main cause of mortality in patients with chronic kidney disease (CKD) [1–3]. Along with the other traditional risk factors, such as age, hypertension (HTN), diabetes mellitus (DM), and uremia-related factors, including inflammation and abnormal bone and mineral metabolism, vascular calcification has been well known to be associated with CVD [4]. Increasing evidence has shown that the process of vascular damage is mediated by proteins, such as alkaline phosphatase, fetuin A, and parathyroid hormone; abnormal calcium and phosphate homeostasis; and protein-bound uremic toxins [5,6]. Pulse wave velocity (PWV) is a noninvasive method to measure vascular function and has been regarded as a strong predictor of CV events and mortality in patients with end-stage renal

disease (ESRD), independent of the classical CV risk factors [2,3]. In the Chronic Renal Insu fficiency Cohort (CRIC) study, CKD patients with high PWV were shown to be more likely to develop adverse renal outcomes, including decrease in renal function by half, ESRD, or death [7].

*<sup>P</sup>*-cresyl sulfate (PC), which is a 188-kDa gut-derived and protein-bound uremic toxin, was shown to progressively accumulate as renal function worsened [8] and has been regarded as a detrimental factor for renal fibrosis by enhancing the production of reactive oxygen species and by activating transforming growth factor β and the renal–angiotensin–aldosterone system [9,10]. Furthermore, PC has been linked with endothelial dysfunction in vitro [11,12], AS, vascular calcification [13], CV events, and even all-cause mortality in patients with CKD and on hemodialysis (HD) [13–15].

Given the aforementioned data, PWV could predict CV morbidity and mortality and PCs could play a role in AS and lead to adverse outcomes. However, the relationship between PCs and carotid–femoral PWV (cfPWV) in a CKD population is unknown. We conducted this study to noninvasively measure vascular function using cfPWV and to examine the possible risk factors, especially serum PC levels, for developing AS in patients on HD.
