title: p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, Division of Nephrology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Björn K I
authors.initials: BK
authors.lastname: Meijers
authors.forename: Henriette
authors.initials: H
authors.lastname: De Loor
authors.forename: Bert
authors.initials: B
authors.lastname: Bammens
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.forename: Yves
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003408:Cresols / Q000097:blood*; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000097:blood*; D014508:Urea / Q000097:blood
chemical_list: D015415:Biomarkers; D003408:Cresols; D012709:Serum Albumin; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D014508:Urea; D007200:Indican