Publication year
2017Source
Clinical Science, 131, 14, (2017), pp. 1631-1647ISSN
Publication type
Article / Letter to editor

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Organization
Nephrology
Pharmacology-Toxicology
Journal title
Clinical Science
Volume
vol. 131
Issue
iss. 14
Page start
p. 1631
Page end
p. 1647
Subject
Radboudumc 11: Renal disorders RIHS: Radboud Institute for Health Sciences; Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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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- Faculty of Medical Sciences [80028]
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