Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

Toxins

Eric Devine²  Detlef H. Krieter³  Marieke Rüth²  Joachim Jankovski¹ 

[1] Medizinische Klinik IV, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Berlin 10117, Germany; E-Mail:;eXcorLab GmbH, Industrie Center Obernburg, Obernburg 63784, Germany; E-Mails:;University Hospital Würzburg, Department of Medicine, Division of Nephrology, Würzburg 97080, Germany; E-Mail:

关键词: kidney disease;    uremic toxin;    protein binding;    ionic strength;    hemodialysis;   

DOI  :  10.3390/toxins6020416

来源: mdpi

【 摘 要 】

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 K_D 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. K_D increased linearly with the NaCl concentration between 0.15 (K_D = 13.2 ± 3.7 µM) and 0.75 M (K_D = 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.