{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:12:49Z","timestamp":1791925969139,"version":"4.3.4"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>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\u2013AHR\u2013TF 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\u20133. 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.<\/jats:p>","DOI":"10.1681\/asn.2017080929","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T09:30:13Z","timestamp":1516181413000},"page":"1063-1072","source":"Crossref","is-referenced-by-count":99,"title":["Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans"],"prefix":"10.1681","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-8644","authenticated-orcid":false,"given":"Vijaya B.","family":"Kolachalama","sequence":"first","affiliation":[{"name":"Section of Computational Biomedicine and"},{"name":"Department of Medicine, Whitaker Cardiovascular Institute, and"},{"name":"Hariri Institute for Computing and Computational Science and Engineering, Boston University, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Shashar","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Alousi","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya","family":"Shivanna","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshab","family":"Rijal","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-6882","authenticated-orcid":false,"given":"Mostafa E.","family":"Belghasem","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Walker","sequence":"additional","affiliation":[{"name":"Renal Section, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Medicine, Whitaker Cardiovascular Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Section of Computational Biomedicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9735-7473","authenticated-orcid":false,"given":"Laura M.","family":"Dember","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte and Hypertension Division, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M.","family":"Francis","sequence":"additional","affiliation":[{"name":"Renal Section, Department of 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