title: Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial.
abstract: The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.9 hours and 30 trial patients who received six-times weekly in-center hemodialysis for an average of 14.6 hours. Metabolomic analysis revealed that increased treatment frequency and time resulted in an average reduction of only 15 percent in the levels of 107 uremic solutes. Quantitative assays confirmed that increased treatment did not significantly reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate. Kinetic modeling suggested that our ability to lower solute concentrations by increasing hemodialysis frequency and duration may be limited by the presence of non-dialytic solute clearances and/or changes in solute production. Thus, failure to achieve larger reductions in uremic solute concentrations may account, in part, for the limited benefits observed with increasing frequency and weekly treatment time in Frequent Hemodialysis Daily Trial participants.
authors.affiliation: The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California, USA. Electronic address: tsirich@stanford.edu.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Sirich
authors.affiliation: The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Fong
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Larive
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Beck
authors.affiliation: The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Renal Research Institute, New York, New York, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Levin
authors.affiliation: Yale New Haven Health System, New Haven, Connecticut, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Kliger
authors.affiliation: The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California, USA.
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Plummer
authors.affiliation: The Departments of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, California, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Meyer
mesh_terms: D000328:Adult; D003408:Cresols / Q000097:blood*; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods*; D013463:Sulfuric Acid Esters / Q000097:blood*; D013997:Time Factors; D014511:Uremia / Q000097:blood*
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican
keywords: hemodialysis; metabolomic; uremic toxins