P-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2009 Oct 17

PMID 19833905

Citations 70

Authors

Bjorn K I Meijers

Henriette de Loor

Bert Bammens

Kristin Verbeke

Yves Vanrenterghem

Pieter Evenepoel

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Indoxyl sulfate and p-cresyl sulfate are important representatives of the protein-bound uremic retention solutes. Serum levels of p-cresyl sulfate and indoxyl sulfate are linked to cardiovascular outcomes and chronic kidney disease progression, respectively. They share important features such as the albumin-binding site, low dialytic clearance, and both originate from protein fermentation. Whether serum concentrations are related is, however, not known.

Design, Setting, Participants, & Measurements: In an observational study in 75 maintenance hemodialysis patients, we studied agreement between indoxyl sulfate and p-cresyl sulfate serum concentrations, dialytic reduction rates, and dialytic clearances. Concentrations were determined by HPLC. Dialytic clearances were determined from total spent dialysate collections. In vitro spiking experiments were performed to explore protein binding characteristics.

Results: Indoxyl sulfate and p-cresyl sulfate total serum concentrations were not related (r = 0.02, P = 0.9), whereas free serum concentrations were only moderately related (r = 0.53, P < 0.001). Indoxyl sulfate and p-cresyl sulfate share the same albumin binding site, for which they are competitive binding inhibitors. Intriguingly, indoxyl sulfate and p-cresyl sulfate reduction rates (r = 0.91, P < 0.001) and dialytic clearances (r = 0.97, P < 0.001) correlated tightly.

Conclusions: Indoxyl sulfate and p-cresyl sulfate serum concentrations are not associated, suggesting different metabolic pathways. Indoxyl sulfate and p-cresyl sulfate are both valid markers to monitor behavior of protein-bound solutes during dialysis. Finally, they are competitive binding inhibitors for the same albumin binding site.

Citing Articles

Validation of an LC-HRMS Method for Quantifying Indoxyl Sulfate and -Cresyl Sulfate in Human Serum.

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Indoxyl Sulfate Induces Ventricular Arrhythmias Attenuated by Secretoneurin in Right Ventricular Outflow Tract Cardiomyocytes.

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Assessment of Within- and Inter-Patient Variability of Uremic Toxin Concentrations in Children with CKD.

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Electrospun EVOH/AST-120 hybrid nanofiber membranes for removal of indoxyl sulfate from blood.

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