title: Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate.
abstract: The protein-bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate to high plasma levels in renal failure and have been associated with adverse events. The clearance of these bound solutes can be altered independently of the urea clearance by changing the dialysate flow and dialyzer size. This study tested whether a sustained difference in clearance would change the plasma levels of PCS and IS.
  
  
  
  Fourteen patients on thrice-weekly nocturnal hemodialysis completed a crossover study of two periods designed to achieve widely different bound solute clearances. We compared the changes in pre-dialysis plasma PCS and IS levels from baseline over the course of the two periods.
  
  
  
  The high-clearance period provided much higher PCS and IS clearances than the low-clearance period (PCS: 23 ± 4 mL/min versus 12 ± 3 mL/min, P < 0.001; IS: 30 ± 5 mL/min versus 17 ± 4 mL/min, P < 0.001). Despite the large difference in clearance, the high-clearance period did not have a different effect on PCS levels than the low-clearance period [from baseline, high: +11% (-5, +37) versus low: -8% (-18, +32), (median, 25th, 75th percentile), P = 0.50]. In contrast, the high-clearance period significantly lowered IS levels compared with the low-clearance period [from baseline, high: -4% (-17, +1) versus low: +22% (+14, +31), P < 0.001). The amount of PCS removed in the dialysate was significantly greater at the end of the high-clearance period [269 (206, 312) versus 199 (111, 232) mg per treatment, P < 0.001], while the amount of IS removed was not different [140 (87, 196) versus 116 (89, 170) mg per treatment, P = 0.15].
  
  
  
  These findings suggest that an increase in PCS generation prevents plasma levels from falling when the dialytic clearance is increased. Suppression of solute generation may be required to reduce plasma PCS levels in dialysis patients.
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Orlando
authors.initials: O
authors.lastname: Camacho
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Rosales
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Shafi
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fullman
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Plummer
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Meyer
authors.affiliation: The Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Sirich
mesh_terms: D015415:Biomarkers / Q000097:blood; D003408:Cresols / Q000097:blood*; D018592:Cross-Over Studies; D015314:Dialysis Solutions / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods*; D051437:Renal Insufficiency / Q000097:blood / Q000628:therapy*; D013463:Sulfuric Acid Esters / Q000097:blood*
chemical_list: D015415:Biomarkers; D003408:Cresols; D015314:Dialysis Solutions; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican
keywords: clearance; p-cresol sulfate; uremia