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The uremic retention solute p-cresyl sulfate and markers of endothelial damage

Björn K I Meijers1, Soetkin Van Kerckhoven, Kristin Verbeke

  • 1Department of Medicine, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
|July 21, 2009
PubMed

Insights

In hemodialysis patients, the uremic toxin p-cresyl sulfate is linked to endothelial microparticle shedding. This suggests p-cresyl sulfate contributes to endothelial dysfunction in chronic kidney disease patients.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Toxicology

Background:

  • Cardiovascular disease is a major concern for chronic kidney disease patients.
  • The uremic retention solute p-cresol is linked to cardiovascular disease in hemodialysis patients.
  • Mechanisms linking p-cresol to cardiovascular disease remain unclear.

Purpose of the Study:

  • To investigate the association between p-cresol and markers of endothelial dysfunction in hemodialysis patients.
  • To determine the direct effects of p-cresol and its derivative p-cresyl sulfate on endothelial cells in vitro.

Main Methods:

  • Prospective observational study of 100 hemodialysis patients.
  • In vitro experiments using human umbilical vein endothelial cells.
  • Measured serum p-cresol, p-cresyl sulfate, soluble P-selectin, and endothelial microparticles.

Main Results:

  • Free serum p-cresol correlated with circulating endothelial microparticles in patients.
  • p-Cresyl sulfate induced dose-dependent shedding of endothelial microparticles in vitro.
  • Rho kinase inhibition blocked p-cresyl sulfate-induced microparticle shedding.

Conclusions:

  • p-Cresyl sulfate promotes endothelial microparticle shedding, suggesting a role in endothelial dysfunction in hemodialysis patients.
  • The in vitro findings indicate p-cresyl sulfate alters endothelial function independently of overt damage.
  • Further mechanistic studies are needed to explore the in vivo relationship.
Abstract

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