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.
Highlights
The use of chronic dialysis in patients with end-stage kidney disease (ESKD) is one of the miracles of modern medicine with which we can keep patients with kidney failure alive; dialysis does not completely remove the many uremic toxins [1]
A role for tryptophan metabolites in chronic kidney disease (CKD). In this issue of the JCI, Arinze et al provide in vivo evidence in mouse and zebrafish animal models that circulating indoxyl sulfate (IS) blocks Wnt signaling in the endothelium and impairs angiogenesis in a Wnt ligand
In a small-nested case-control study, the authors found that concentrations of IS and other tryptophan metabolites were higher in CKD patients with peripheral arterial disease (PAD) who developed adverse limb events compared with those in individuals that had PAD without adverse events
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 (CKDassociated) 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
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