{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:49:47Z","timestamp":1789080587247,"version":"build-2803163510"},"reference-count":149,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"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>Chronic kidney disease (CKD) is associated with the systemic accumulation of uremic toxins (UTs) due to impaired renal elimination. Among these, indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are particularly challenging because of their high protein binding and limited removal by dialysis. In addition to renal excretion, the transport of IS and PCS, and their microbiota-derived precursors, indole and p-cresol, across key physiological barriers\u2014the intestinal barrier, blood\u2013brain barrier, and renal proximal tubule\u2014critically influences their distribution and elimination. This review provides an overview of transporter-mediated mechanisms involved in the disposition of IS, PCS, and their microbial precursors, indole and p-cresol. It also examines how these UTs may interact with commonly prescribed drugs in CKD, particularly those that share transporter pathways as substrates or inhibitors. These drug\u2013toxin interactions may influence the pharmacokinetics and toxicity of IS and PCS, but remain poorly characterized and largely overlooked in clinical settings. A better understanding of these processes may guide future efforts to optimize pharmacotherapy and support more informed management of CKD patients, particularly in the context of polypharmacy.<\/jats:p>","DOI":"10.3390\/ijms26136328","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transporter-Mediated Interactions Between Uremic Toxins and Drugs: A Hidden Driver of Toxicity in Chronic Kidney Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9853-3266","authenticated-orcid":false,"given":"Pierre","family":"Spicher","sequence":"first","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Blood-Brain Barrier Laboratory (LBHE), UR 2465, University of Artois, F-62300 Lens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-4389","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Brazier","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Department of Nephrology, Amiens University Medical Center, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0214-5567","authenticated-orcid":false,"given":"Sol\u00e8ne M.","family":"Laville","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Department of Clinical Pharmacology, Amiens University Medical Center, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5384-9006","authenticated-orcid":false,"given":"Sophie","family":"Liabeuf","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Department of Clinical Pharmacology, Amiens University Medical Center, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Kamel","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Department of Clinical Biochemistry, Amiens University Medical Center, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-0867","authenticated-orcid":false,"given":"Maxime","family":"Culot","sequence":"additional","affiliation":[{"name":"Blood-Brain Barrier Laboratory (LBHE), UR 2465, University of Artois, F-62300 Lens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bodeau","sequence":"additional","affiliation":[{"name":"MP3CV Laboratory, UR7517, Jules Verne University of Picardie, F-80000 Amiens, France"},{"name":"Department of Clinical Pharmacology, Amiens University Medical Center, F-80000 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.semnephrol.2018.02.004","article-title":"Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease","volume":"38","author":"Chillon","year":"2018","journal-title":"Semin. 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