In patients with chronic kidney disease (CKD), adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds with intrinsic biological activities, many of which are too large to be filtered and/or are protein bound. The renal excretion of protein-bound toxins depends largely on active tubular secretion, which shifts the binding and allows for active secretion of the free fraction. To facilitate this process, renal proximal tubule cells are equipped with a range of transporters that co-operate in basolateral uptake and luminal excretion. Many of these transporters have been characterized as mediators of drug disposition, but have recently been recognized for their importance in the proximal renal tubular transport of uremic toxins as well. This also indicates that during uremia, drug disposition may be severely affected as a result of drug–uremic toxin interaction. In addition, CKD patients receive various drugs to treat their complications potentially resulting in drug–drug interactions (DDIs), also for drugs that are non-renally excreted. This review discusses the current knowledge on formation, disposition and removal of protein-bound uremic toxins. Furthermore, implications associated with drug treatment in kidney failure, as well as innovative renal replacement therapies targetting the protein-bound uremic toxins are being discussed. It will become clear that the complex problems associated with uremia warrant a transdisciplinary approach that unites research experts in the area of fundamental biomedical research with their colleagues in clinical nephrology.
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July 2017
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This issue of Clinical Science showcases review articles covering kidney disease, the respiratory system, neurology and oxidative stress.
Review Article|
June 30 2017
Disposition and clinical implications of protein-bound uremic toxins
Jitske Jansen;
Jitske Jansen
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
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Joachim Jankowski;
Joachim Jankowski
2Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
3Department of Pathology, University of Maastricht, CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands
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Prathibha R. Gajjala;
Prathibha R. Gajjala
2Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
3Department of Pathology, University of Maastricht, CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands
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Jack F.M. Wetzels;
Jack F.M. Wetzels
4Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
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Rosalinde Masereeuw
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Correspondence: Rosalinde Masereeuw ([email protected])
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Publisher: Portland Press Ltd
Received:
January 31 2017
Revision Received:
April 10 2017
Accepted:
April 11 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (14): 1631–1647.
Article history
Received:
January 31 2017
Revision Received:
April 10 2017
Accepted:
April 11 2017
Citation
Jitske Jansen, Joachim Jankowski, Prathibha R. Gajjala, Jack F.M. Wetzels, Rosalinde Masereeuw; Disposition and clinical implications of protein-bound uremic toxins. Clin Sci (Lond) 15 July 2017; 131 (14): 1631–1647. doi: https://doi.org/10.1042/CS20160191
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