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p-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients

Björn K. I. Meijers^*, Henriette De Loor^*, Bert Bammens^*, Kristin Verbeke, Yves Vanrenterghem^*, and Pieter Evenepoel^*

^* Department of Medicine, Division of Nephrology and Laboratory for Gastro-Intestinal Research and Leuven Food Science and Nutrition Research Centre, University Hospital Leuven, Leuven, Belgium

Correspondence: Dr. P. Evenepoel, Dienst nefrologie, Universitair Ziekenhuis Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Phone: 32-16-344591; Fax: 32-16-344599; E-mail: pieter.evenepoel{at}uz.kuleuven.ac.be

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.