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Toxins 2014, 6(2), 416-429;

Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

eXcorLab GmbH, Industrie Center Obernburg, Obernburg 63784, Germany
University Hospital Würzburg, Department of Medicine, Division of Nephrology, Würzburg 97080, Germany
Medizinische Klinik IV, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Berlin 10117, Germany
Author to whom correspondence should be addressed.
Received: 9 November 2013 / Revised: 13 January 2014 / Accepted: 14 January 2014 / Published: 24 January 2014
(This article belongs to the Special Issue Uremic Toxins)
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Protein binding prevents uremic toxins from removal by conventional extracorporeal therapies leading to accumulation in maintenance dialysis patients. Weakening of the protein binding may enhance the dialytic elimination of these toxins. In ultrafiltration and equilibrium dialysis experiments, different measures to modify the plasma binding affinity and capacity were tested: (i), increasing the sodium chloride (NaCl) concentration to achieve a higher ionic strength; (ii), increasing the temperature; and (iii), dilution. The effects on the dissociation constant KD and the protein bound fraction of the prototypical uremic toxin indoxyl sulfate (IS) in plasma of healthy and uremic individuals were studied. Binding of IS corresponded to one site binding in normal plasma. KD increased linearly with the NaCl concentration between 0.15 (KD = 13.2 ± 3.7 µM) and 0.75 M (KD = 56.2 ± 2.0 µM). Plasma dilution further reduced the protein bound toxin fraction by lowering the protein binding capacity of the plasma. Higher temperatures also decreased the protein bound fraction of IS in human plasma. Increasing the NaCl concentration was effective to weaken the binding of IS also in uremic plasma: the protein bound fraction decreased from 89% ± 3% to 81% ± 3% at 0.15 and 0.75 M NaCl, respectively. Dilution and increasing the ionic strength and temperature enhance the free fraction of IS allowing better removal of the substance during dialysis. Applied during clinical dialysis, this may have beneficial effects on the long-term outcome of maintenance dialysis patients. View Full-Text
Keywords: kidney disease; uremic toxin; protein binding; ionic strength; hemodialysis kidney disease; uremic toxin; protein binding; ionic strength; hemodialysis

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Devine, E.; Krieter, D.H.; Rüth, M.; Jankovski, J.; Lemke, H.-D. Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate. Toxins 2014, 6, 416-429.

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