{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:38:52Z","timestamp":1790912332308,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Njurfonden (Swedish Renal foundation)","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}]},{"name":"Hj\u00e4rt lungfonden","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}]},{"name":"CIMED","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}]},{"name":"ALF","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AstraZeneca","award":["2018-00932 GOING-FWD"],"award-info":[{"award-number":["2018-00932 GOING-FWD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We hypothesized that patients with chronic kidney disease (CKD) display an altered plasma amino acid (AA) metabolomic profile that could contribute to abnormal vascular maintenance of peripheral circulation in uremia. The relationships between plasma AAs and endothelial and vascular smooth muscle function in the microcirculation of CKD patients are not well understood. The objective of this study is to investigate to what extent the levels of AAs and its metabolites are changed in CKD patients and to test their relationship with endothelial and vascular smooth muscle function. Patients with CKD stages 3 and 5 and non-CKD controls are included in this study. We report that there was a significant reduction of the biopterin (BH4\/BH2) ratio, which was accompanied by increased plasma levels of BH2, asymmetric dimethylarginine (ADMA) and citrulline in patients with CKD-5 vs. CKD-3 vs. controls. In vivo augmentation index measurement showed a positive association with ADMA in all participants. The contribution of nitric oxide, assessed by ex vivo assay, showed a negative association with creatinine, ADMA and citrulline in all participants. In CKD-5, BH4 negatively correlated with ADMA and ornithine levels, and the ex vivo endothelium-mediated dilatation positively correlated with phenylalanine levels. In conclusion, uremia is associated with alterations in AA metabolism that may affect endothelium-dependent dilatation and vascular stiffness in microcirculation. Interventional strategies aiming to normalize the AA metabolism could be of interest as treatment options.<\/jats:p>","DOI":"10.3390\/ijms24065582","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"5582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-9100","authenticated-orcid":false,"given":"Samsul","family":"Arefin","sequence":"first","affiliation":[{"name":"Department of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"L\u00f6fgren","sequence":"additional","affiliation":[{"name":"Early CVRM, BioPharmaceuticals R&D, AstraZeneca, 431 50 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-4820","authenticated-orcid":false,"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna B.","family":"Granqvist","sequence":"additional","affiliation":[{"name":"Early CVRM, BioPharmaceuticals R&D, AstraZeneca, 431 50 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-6836","authenticated-orcid":false,"given":"Karolina","family":"Kublickiene","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","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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