Toxins 2014, 6(2), 416-429; doi:10.3390/toxins6020416
Article

Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

Received: 9 November 2013; in revised form: 13 January 2014 / Accepted: 14 January 2014 / Published: 24 January 2014
(This article belongs to the Special Issue Uremic Toxins)
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.
Abstract: 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.
Keywords: kidney disease; uremic toxin; protein binding; ionic strength; hemodialysis
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MDPI and ACS Style

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.

AMA Style

Devine E, Krieter DH, Rüth M, Jankovski J, Lemke H-D. Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate. Toxins. 2014; 6(2):416-429.

Chicago/Turabian Style

Devine, Eric; Krieter, Detlef H.; Rüth, Marieke; Jankovski, Joachim; Lemke, Horst-Dieter. 2014. "Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate." Toxins 6, no. 2: 416-429.

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