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Indoxyl Sulfate, a Uremic Endotheliotoxin

by Guillaume Lano 1, Stéphane Burtey 1,2,*,† and Marion Sallée 1,2,†
C2VN, Aix Marseille Univ, INSERM, INRAE, 13005 Marseille, France
Centre de Néphrologie et Transplantation Rénale, AP-HM, Hôpital de la Conception, 147 Bd Baille, 13005 Marseille, France
Author to whom correspondence should be addressed.
For the French Renal Endothelial Society (FRENDS).
Toxins 2020, 12(4), 229;
Received: 19 February 2020 / Revised: 2 April 2020 / Accepted: 3 April 2020 / Published: 5 April 2020
(This article belongs to the Special Issue Uremic Toxin-Mediated Mechanisms in Cardiovascular and Renal Disease)
Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)—derived from tryptophan metabolism—accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-κB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients. View Full-Text
Keywords: chronic kidney disease; indoxyl sulfate; cardiovascular disease; endothelial dysfunction; aryl hydrocarbon receptor chronic kidney disease; indoxyl sulfate; cardiovascular disease; endothelial dysfunction; aryl hydrocarbon receptor
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Lano, G.; Burtey, S.; Sallée, M. Indoxyl Sulfate, a Uremic Endotheliotoxin. Toxins 2020, 12, 229.

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