p-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients

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.

The Production of p-Cresol Sulfate and Indoxyl Sulfate in Vegetarians Versus Omnivores

“…These findings, coupled with knowledge that the enzymes that produce p-cresol and indole are irregularly present among the myriad types of colon microbes, could account for many features of PCS and IS production (28,29). As observed in prior studies, we found that PCS and IS production rates were poorly correlated in individual participants, which could be explained by differences in the microbial flora of different individuals (30). In addition, the variation in PCS and IS production among individuals was much larger than the variation in urea production, and the correlations between PCS and IS production and protein and fiber intake were weak.…”

Grape seed proanthocyanidin extract protects human umbilical vein endothelial cells from indoxyl sulfate-induced injury via ameliorating mitochondrial dysfunction

“…7,8 As a consequence, decrease in concentration of intestinally generated uremic retention solutes, like indole, by the intestinal sorbent AST-120 (Kremezin) has been accepted in mostly Asian countries as a strategy to restrain the progression of CKD. In a recent large randomized controlled trial in the United States and Europe, however, this positive effect could not be confirmed.…”

“…[4][5][6] Dialysis is usually not powerful to remove protein-bound uremic toxins alone. 7,8 AST-120 (Kremezin), however, in a recent large randomized controlled trial in the United States and Europe, the positive effect of removing indoxyl sulfate could not be confirmed.…”

p-Cresol and Cardiovascular Risk in Mild-to-Moderate Kidney Disease

“…More recently, a direct association between indoxyl sulfate and cardiovascular outcomes was observed (13). Intriguingly, whereas p-cresyl sulfate and indoxyl sulfate behave similarly during dialysis and share the same albumin binding site, total serum concentrations in hemodialysis patients are unrelated (14).…”