Vascular Incompetence in Dialysis Patients-Protein-Bound Uremic Toxins and Endothelial Dysfunction

Abstract : Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium-dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia-specific factors. Several uremic toxins, mostly protein-bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p-cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro-oxidant and pro-inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein-bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.
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Contributeur : Laetitia Dou <>
Soumis le : mercredi 4 octobre 2017 - 17:27:07
Dernière modification le : lundi 23 avril 2018 - 14:30:04

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Noémie Jourde-Chiche, Laetitia Dou, Claire Cerini, Françoise Dignat-George, Philippe Brunet. Vascular Incompetence in Dialysis Patients-Protein-Bound Uremic Toxins and Endothelial Dysfunction. Seminars in Dialysis, Wiley, 2011, 24 (3), pp.327-337. 〈10.1111/j.1525-139X.2011.00925.x〉. 〈hal-01610435〉



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