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Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes

Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium
Department of Pharmaceutical Sciences, Pharmacology, Utrecht University, 3584 CG Utrecht, The Netherlands
Otto Loewi Research Center, Physiology, Medical University of Graz, 8010 Graz, Austria
Author to whom correspondence should be addressed.
Toxins 2019, 11(7), 385;
Received: 5 May 2019 / Revised: 13 June 2019 / Accepted: 27 June 2019 / Published: 1 July 2019
(This article belongs to the Special Issue Disposition of Uremic Toxins: The Challenges in Uremia)
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To better understand the kinetics of protein-bound uremic toxins (PBUTs) during hemodialysis (HD), we investigated the distribution of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (pCS) in erythrocytes of HD patients. Their transport across the erythrocyte membrane was explored in the absence of plasma proteins in vitro in a series of loading and unloading experiments of erythrocytes from healthy subjects and HD patients, respectively. Furthermore, the impact of three inhibitors of active transport proteins in erythrocytes was studied. The four PBUTs accumulated in erythrocytes from HD patients. From loading and unloading experiments, it was found that (i) the rate of transport was dependent on the studied PBUT and increased in the following sequence: HA < IS < pCS < IAA and (ii) the solute partition of intra- to extra-cellular concentrations was uneven at equilibrium. Finally, inhibiting especially Band 3 proteins affected the transport of HA (both in loading and unloading), and of IS and pCS (loading). By exploring erythrocyte transmembrane transport of PBUTs, their kinetics can be better understood, and new strategies to improve their dialytic removal can be developed. View Full-Text
Keywords: protein-bound uremic toxins; hippuric acid; indole-3-acetic acid; indoxyl sulfate; p-cresyl sulfate; erythrocyte; DIDS; MK571; KO143; hemodialysis; chronic kidney disease protein-bound uremic toxins; hippuric acid; indole-3-acetic acid; indoxyl sulfate; p-cresyl sulfate; erythrocyte; DIDS; MK571; KO143; hemodialysis; chronic kidney disease

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Deltombe, O.; Glorieux, G.; Marzouki, S.; Masereeuw, R.; Schneditz, D.; Eloot, S. Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins 2019, 11, 385.

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