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. 2009 Dec;4(12):1932-8.
doi: 10.2215/CJN.02940509. Epub 2009 Oct 15.

p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients

Björn K I Meijers  1 , Henriette De Loor, Bert Bammens, Kristin Verbeke, Yves Vanrenterghem, Pieter Evenepoel
Affiliations

p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients

Björn K I Meijers et al. Clin J Am Soc Nephrol. 2009 Dec.

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.

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Figures

Figure 1.
Figure 1.
Flow chart showing patient screening and inclusion.
Figure 2.
Figure 2.
Agreement between (A) total serum concentrations, (B) free serum concentrations, and (C) free fractions of p-cresyl sulfate and indoxyl sulfate in a cohort of 75 hemodialysis patients. Spearman correlation coefficients are reported.
Figure 3.
Figure 3.
Agreement between reduction rates of (A) p-cresyl sulfate and indoxyl sulfate, (B) urea and creatinine, (C) urea and indoxyl sulfate, and (D) urea and p-cresyl sulfate in a cohort of 75 hemodialysis patients. Spearman correlation coefficients are reported.
Figure 4.
Figure 4.
Agreement between dialytic clearances of (A) p-cresyl sulfate and indoxyl sulfate, (B) urea and creatinine, (C) urea and indoxyl sulfate, and (D) urea and p-cresyl sulfate in a cohort of 75 hemodialysis patients. Spearman correlation coefficients are reported.
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