{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:01Z","timestamp":1792092121950,"version":"4.4.0"},"reference-count":138,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"crossref","award":["22OP+059"],"award-info":[{"award-number":["22OP+059"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","award":["101099092"],"award-info":[{"award-number":["101099092"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Strategic alliance of the University of Twente, University of Utrecht, and University Medical Center Utrecht, of the Dutch organization for Scientific Research","award":["20775"],"award-info":[{"award-number":["20775"]}]},{"name":"Kidney Innovation Accelerator KidneyX prize"},{"name":"Dutch national growth fund"},{"name":"European Renal Association-European Dialysis Transplantation Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In this review, PBUT removal with current state-of-the-art dialysis technologies and future perspectives are discussed. Strategies to enhance PBUT clearance include methods that interfere with PBUT\u2013albumin binding, such as chemical displacers, high ionic strength, pH changes, or electromagnetic fields, thereby increasing the free fraction available for dialysis. While these methods have shown promise in vitro, and some also in vivo, long-term safety data are lacking. PBUT removal can also be increased by adsorption, either directly via hemoperfusion, or indirectly, e.g., via sorbents incorporated in a mixed-matrix membrane or dissolved in the dialysate. In the kidney, PBUTs are secreted in the proximal tubules; hence, a cell-based bioartificial kidney (BAK) that secretes PBUTs is proposed as an add-on to current dialysis. Yet both PBUT adsorption strategies and, in particular, BAKs face considerable challenges in upscaling and mass production at acceptable costs. In conclusion, many novel technologies are under development, all requiring further (pre)clinical testing and upscaling before these strategies can be applied in the clinic.<\/jats:p>","DOI":"10.3390\/toxins18010057","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:35:56Z","timestamp":1769193356000},"page":"57","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Strategies for Removal of Protein-Bound Uremic Toxins in Hemodialysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Joost C.","family":"de Vries","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7238-1998","authenticated-orcid":false,"given":"Jo\u00e3o G.","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert M.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-3509","authenticated-orcid":false,"given":"Jeroen C.","family":"Vollenbroek","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"BIOS Lab on a Chip Group, Faculty of EEMCS, University of Twente, 7500 AE Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7759-7816","authenticated-orcid":false,"given":"Fokko P.","family":"Wieringa","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"IMEC the Netherlands\u2014Health Research, 5656 AE Eindhoven, The Netherlands"},{"name":"European Kidney Health Alliance (EKHA, WG3), 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Aachen-Maastricht Institute for Cardiorenal Disease (AMICARE), University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-6428","authenticated-orcid":false,"given":"Marianne C.","family":"Verhaar","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-2442","authenticated-orcid":false,"given":"Dimitrios","family":"Stamatialis","sequence":"additional","affiliation":[{"name":"Advanced Organ Bioengineering and Therapeutics, Faculty of Science and Technology, Technical Medical Centre, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-1074","authenticated-orcid":false,"given":"Rosalinde","family":"Masereeuw","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1917-6255","authenticated-orcid":false,"given":"Karin G. F.","family":"Gerritsen","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Pletinck, A., Schepers, E., and Glorieux, G. (2018). 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