ArticleJournal of the American Society of Nephrology : JASN2018
Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans.
Article in Journal of the American Society of Nephrology : JASN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 98 citations in OpenAlex.
- The association between serum indoxyl sulfate and radial-cephalic arteriovenous fistulas dysfunction in ESKD patients: a prospective study.Renal failure · 2026Article
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- Selected tryptophan metabolites and inflammatory molecules in hemodialyzed patients.Pharmacological reports : PR · 2026Article
- Tryptophan metabolism reprogramming potentially contributes to the prothrombotic milieu in mice and humans with SARS-CoV-2.Blood vessels, thrombosis & hemostasis · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Dietary tryptophan augments cancer-associated venous thrombogenicity mitigated by indoleamine 2,3-dioxygenase 1 inhibition.Blood advances · 2025Article
- Observational
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- Activation and targetability of TYMP-IL-6-TF signaling in the skin microenvironment in uremic calciphylaxis.Science translational medicine · 2025Article
- Amino acid metabolism in kidney health and disease.Nature reviews. Nephrology · 2024Review
- Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation ofPharmaceutics · 2024Review
- A tryptophan-derived uremic metabolite/Ahr/Pdk4 axis governs skeletal muscle mitochondrial energetics in chronic kidney disease.JCI insight · 2024Article
- Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure.Toxicological research · 2024Article
- Natural antagonistic flavones for AhR inhibit indoxyl sulfate-induced inflammatory gene expressionFood & nutrition research · 2024Article
- Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease.Clinical kidney journal · 2024Article
- Temporal serum metabolomic and lipidomic analyses distinguish patients with access-related hand disability following arteriovenous fistula creation.Scientific reports · 2023Article
- Tryptophan Metabolites Target Transmembrane and Immunoglobulin Domain-Containing 1 Signaling to Augment Renal Tubular Injury.The American journal of pathology · 2023Article
- Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease.Circulation research · 2023Article
- Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence.International journal of molecular sciences · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute-AHR-TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2-3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.
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