Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), whilst CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney, but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neuro-hormonal, mechanical and biochemical factors, the non-dialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo and clinical observations. PBUTs are ineffectively removed by hemodialysis because their complexes with albumins are larger than the pores of the dialysis membranes. PBUTs such as indoxyl sulfate (IS) and p-cresyl sulfate (p-CS) are key determinate and predictive factors for the progression of CVD in CKD patients. In CRS, both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) exhibit significant dysfunction which is associated with the progression of CVD. PBUTs influence proliferation, calcification, senescence, migration, inflammation and oxidative stress in VSMCs and ECs through various mechanisms. These pathological changes lead to arterial remodeling, stiffness and atherosclerosis, thus, reduce heart perfusion and impair left ventricular function, aggravating CRS. There is limited literature about PBUTs' effect on the vascular system and their contribution to CRS. This review summarizes current knowledge on how PBUTs influence vasculature, clarifies the relationship between uremic toxins related vascular disease and CRS, and highlights the potential therapeutic strategies of uremic vasculopathy in the setting of CRS.
- Protein-bound uremic toxins
- vascular smooth muscle cells
- endothelial cells
- cardiorenal syndrome
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology