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Toxins 2015, 7(10), 3933-3946; doi:10.3390/toxins7103933

Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis

1
Department of Internal Medicine, Nephrology Section, Ghent University Hospital, Ghent 9000, Belgium
2
Division of Nephrology, Amiens University Hospital, Amiens 80000, France
*
Author to whom correspondence should be addressed.
Academic Editor: C. Chris Yun
Received: 6 August 2015 / Revised: 16 September 2015 / Accepted: 22 September 2015 / Published: 28 September 2015
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Abstract

As protein binding of uremic toxins is not well understood, neither in chronic kidney disease (CKD) progression, nor during a hemodialysis (HD) session, we studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5 patients and ten stable hemodialysis patients were included. Blood samples were taken either during the routine ambulatory visit (CKD patients) or from blood inlet and outlet line during dialysis (HD patients). Total (CT) and free concentrations were determined of p-cresylglucuronide (pCG), hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS) and p-cresylsulfate (pCS), and their percentage protein binding (%PB) was calculated. In CKD patients, %PB/CT resulted in a positive correlation (all p < 0.001) with renal function for all five uremic toxins. In HD patients, %PB was increased after 120 min of dialysis for HA and at the dialysis end for the stronger (IAA) and the highly-bound (IS and pCS) solutes. During one passage through the dialyzer at 120 min, %PB was increased for HA (borderline), IAA, IS and pCS. These findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that (i) only the free fraction can pass the filter and (ii) the equilibrium, as it was pre-dialysis, cannot be restored during the dialysis session, as it is continuously disturbed. View Full-Text
Keywords: chronic kidney disease; hemodialysis; protein binding; uremic toxins; p-cresylglucuronide; hippuric acid; indole-3-acetic acid; indoxyl sulfate; p-cresylsulfate chronic kidney disease; hemodialysis; protein binding; uremic toxins; p-cresylglucuronide; hippuric acid; indole-3-acetic acid; indoxyl sulfate; p-cresylsulfate
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Deltombe, O.; Van Biesen, W.; Glorieux, G.; Massy, Z.; Dhondt, A.; Eloot, S. Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis. Toxins 2015, 7, 3933-3946.

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