{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:59:51Z","timestamp":1787792391669,"version":"build-2784847793"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The impact of protein bound uremic toxins (PBUTs) and lymphocyte alterations in morbidity and mortality in patients on hemodialysis (HD) is of great concern. The aim of this study was the assessment of association between PBUTs, immunosenescent lymphocytes\u2019 phenotype and clinical events [cardiovascular, severe infections (hospitalization due to infection, respiratory infection), all-cause mortality] during 2-year follow-up. In this prospective observational study, lymphocytes\u2019 phenotype of 54 patients on HD and 31 age-matched controls was analyzed by flow cytometry, and simultaneously, PBUT serum levels [hippuric acid (HA), indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glycuronide (pCG), in-dole-3-acetic acid (IAA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)] were quantified by ultra-performance liquid chromatography. Patients with increased levels of free IxS and total and free HA had higher mortality within a 2-year follow-up period (p = 0.049, p = 0.01, p = 0.01, respectively). In patients who experienced cardiovascular events, higher concentrations of CMPF (p = 0.015) were observed. Higher total and free HA levels associate with increased all-cause mortality in patients on HD, independently of age, dialysis vintage, and decreased count of CD4+CD45RA+CD31+ and na\u00efve B cells (CD19+IgD+CD27\u2212). In patients on HD, increased levels of total and free HA associate with an increased risk of death.<\/jats:p>","DOI":"10.3390\/ijms262110376","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:51:42Z","timestamp":1761526302000},"page":"10376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lymphocyte Phenotypes and Protein-Bound Uremic Toxins as Determinants of Clinical Outcomes in Hemodialysis Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3935-8363","authenticated-orcid":false,"given":"Theodoros","family":"Tourountzis","sequence":"first","affiliation":[{"name":"Protypo Dialysis Center of Thessaloniki, 55535 Thessaloniki, Greece"},{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Lioulios","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-9274","authenticated-orcid":false,"given":"Stamatia","family":"Stai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-8491","authenticated-orcid":false,"given":"Steven Van","family":"Laecke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Nephrology Unit, Ghent University Hospital, 9000 Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-7173","authenticated-orcid":false,"given":"Eleni","family":"Moysidou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9565-6931","authenticated-orcid":false,"given":"Michalis","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadni","family":"Fouza","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asimina","family":"Fylaktou","sequence":"additional","affiliation":[{"name":"Department of Immunology, National Peripheral Histocompatibility Center, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantia","family":"Kantartzi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7641-4707","authenticated-orcid":false,"given":"Griet","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Nephrology Unit, Ghent University Hospital, 9000 Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-9863","authenticated-orcid":false,"given":"Maria","family":"Stangou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokratio\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ijcard.2017.02.095","article-title":"Risk Factors for Mortality in Patients Undergoing Hemodialysis: A Systematic Review and Meta-Analysis","volume":"238","author":"Ma","year":"2017","journal-title":"Int. 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