Vasculopathy in the setting of cardiorenal syndrome: Roles of protein-bound uremic toxins

Jingbin Guo, Lu Lu, Yue Hua, Kevin Huang, Ian Wang, Li Huang, Qiang Fu, Aihua Chen, Paul Chan, Huimin Fan, Zhong Min Liu, Bing Hui Wang

Research output: Contribution to journalReview articlepeer-review

33 Citations (Scopus)


Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), while 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, neurohormonal, mechanical, and biochemical factors, nondialyzable 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 and p-cresyl sulfate 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 that 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 and thus reduce heart perfusion and impair left ventricular function, aggravating CRS. There is limited literature about the effect of PBUT on the vascular system and their contribution to CRS. This review summarizes current knowledge on how PBUTs influence vasculature, clarifies the relationship between uremic toxin-related vascular disease and CRS, and highlights the potential therapeutic strategies of uremic vasculopathy in the setting of CRS.

Original languageEnglish
Pages (from-to)H1-H13
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1
Publication statusPublished - 2017


  • Cardiorenal syndrome
  • Endothelial cells
  • Protein-bound uremic toxins
  • Vascular smooth muscle cells
  • Vasculopathy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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