Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp positive correlation between chronic kidney disease (CKD) and cardiovascular disease (CVD) has been demonstrated, but the causative role of uremic toxin remains unclear. 1-3 A number of retention compounds act as uremic toxins, accumulating in the blood of CKD patient, and elevated circulating uremic toxins negatively affect biological function through induction of oxidative stress. The removal of uremic solutes, therefore, has the potential to prevent CVD. However, protein-bound retention solutes are insufficiently eliminated even by hemodialysis. 4-6 Indoxyl sulfate (IS) is a protein-bound uremic toxin metabolized in the liver from indole, a tryptophan metabolite that is formed by intestinal bacteria. Together with CKD progression, IS accumulates in the blood, which leads to cellular toxicity by inducing oxidative stress. 7In particular, recent studies have suggested that IS is associated with vascular damage by inducing vasoactive substances related to atherogenesis such as chemokines, cytokines or cell adhesion molecules. 8,9 As a possible mechanism of the process, we previously demonstrated that IS mediates monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVECs) by producing reactive oxygen species (ROS) through NADPH oxidase activation. 10 MCP-1 is a chemokine that is involved in early stage of atherosclerosis through the recruitment of monocytes from the blood stream to the subendothelial space. 11-13 Moreover, others have shown that IS-induced vascular damage exhibits inflammatory effects in monocytes, vascular smooth muscle cells or cardiac myocytes.