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Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.<\/jats:p>","DOI":"10.3390\/ijms24043640","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"3640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5880-885X","authenticated-orcid":false,"given":"Sam","family":"Hobson","sequence":"first","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samsul","family":"Arefin","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awahan","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-1626","authenticated-orcid":false,"given":"Leah","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-9276","authenticated-orcid":false,"given":"Thomas","family":"Ebert","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-6340","authenticated-orcid":false,"given":"Henriette","family":"de Loor","sequence":"additional","affiliation":[{"name":"Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Evenepoel","sequence":"additional","affiliation":[{"name":"Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, University Hospitals Leuven, BE-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-4820","authenticated-orcid":false,"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Kublickiene","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska, Institutet, 141 52 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.kint.2019.07.012","article-title":"A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases","volume":"96","author":"Jager","year":"2019","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: An update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. 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