Indoxyl sulfate in uremia: an old idea with updated concepts

Patients with end-stage kidney disease (ESKD) have increased vascular disease. While protein-bound molecules that escape hemodialysis may contribute to uremic toxicity, specific contributing toxins remain ambiguous. In this issue of the JCI, Arinze et al. explore the role of tryptophan metabolites i...

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Bibliographic Details
Main Authors: Anders H. Berg, Sanjeev Kumar, S. Ananth Karumanchi
Format: Article
Language:English
Published: American Society for Clinical Investigation 2022-01-01
Series:The Journal of Clinical Investigation
Online Access:https://doi.org/10.1172/JCI155860
Description
Summary:Patients with end-stage kidney disease (ESKD) have increased vascular disease. While protein-bound molecules that escape hemodialysis may contribute to uremic toxicity, specific contributing toxins remain ambiguous. In this issue of the JCI, Arinze et al. explore the role of tryptophan metabolites in chronic kidney disease–associated (CKD-associated) peripheral arterial disease. The authors used mouse and zebrafish models to show that circulating indoxyl sulfate (IS) blocked endothelial Wnt signaling, which impaired angiogenesis. Plasma levels of IS and other tryptophan metabolites correlated with adverse peripheral vascular disease events in humans. These findings suggest that lowering IS may benefit individuals with CKD and ESKD.
ISSN:1558-8238