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Indoxyl sulfate in uremia: an old idea with updated concepts
Anders H. Berg, … , Sanjeev Kumar, S. Ananth Karumanchi
Anders H. Berg, … , Sanjeev Kumar, S. Ananth Karumanchi
Published January 4, 2022
Citation Information: J Clin Invest. 2022;132(1):e155860. https://doi.org/10.1172/JCI155860.
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Commentary

Indoxyl sulfate in uremia: an old idea with updated concepts

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Abstract

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.

Authors

Anders H. Berg, Sanjeev Kumar, S. Ananth Karumanchi

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Figure 1

Model of IS synthesis and accumulation in CKD.

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Model of IS synthesis and accumulation in CKD.
Gut-residing bacteria pro...
Gut-residing bacteria produce IS from dietary tryptophan. The hydrophobicity of IS and other tryptophan derivatives favors binding to proteins in the circulation. With CKD, large molecules remain unfiltered by the kidney or dialysis. Consequently, circulating IS accumulates. Increased IS levels activate endothelial AhRs, which suppress the Wnt pathway and damage the vasculature.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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