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Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate.
MedLine Citation:
PMID:  23300093     Owner:  NLM     Status:  Publisher    
Indoxyl sulfate and p-cresyl sulfate are two uremic retention solutes implicated in the uremic syndrome. Removal during dialysis is limited, mainly due to protein binding. Binding characteristics to healthy albumin have recently been characterized. Whether uremia alters the binding characteristics of albumin, is currently unknown. Moreover, protein binding values previously determined with ultrafiltration are in sharp contrast to recently reported values based on microcalorimetry. In the present study, indoxyl sulfate and p-cresyl sulfate binding were therefore quantified using both equilibrium dialysis and ultrafiltration. Deming regression demonstrated good agreement between equilibrium dialysis and ultrafiltration. Free serum concentrations of indoxyl sulfate (+26.6%) and p-cresyl sulfate (+19.7%) were slightly higher at body temperature as compared to room temperature. To investigate binding kinetics, we titrated plasma of healthy individuals or hemodialysis patients and albumin solutions. Theoretical models of protein binding were fitted to observed titration curves. Binding coefficients of both toxins were highest in purified albumin, and were reduced from healthy to uremic plasma. In conclusion, the ultrafiltration-HPLC technique reliably measures free serum concentrations of indoxyl sulfate and p-cresyl sulfate. Albumin is the main binding protein, both in health and in advanced stages of chronic kidney disease. Modeling suggests that albumin contains two binding sites for both toxins, a single high affinity binding site and a second low affinity binding site. The high affinity binding site accounts for at least 90% of overall binding. Competition for this binding site could be used to augment free solute concentrations during dialysis, thus improving epuration. Copyright © 2013 John Wiley & Sons, Ltd.
Liesbeth Viaene; Pieter Annaert; Henriette de Loor; Ruben Poesen; Pieter Evenepoel; Björn Meijers
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  -     ISSN:  1099-081X     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 John Wiley & Sons, Ltd.
Nephrology, University Hospitals Leuven, Belgium; Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Belgium.
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