title: Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration.
abstract: BACKGROUND
  The accumulation of larger and protein-bound toxins is involved in the uraemic syndrome but their elimination by dialysis therapy remains difficult. In the present study, the impact of the albumin permeability of recently introduced advanced high-flux dialysis membranes on the removal of such substances was tested in haemodialysis and online post-dilution haemodiafiltration.
  
  
  METHODS
  Two types of polyethersulfone membranes only differing in albumin permeability (referred as PU- and PU+) were compared in eight patients on maintenance dialysis in a prospective cross-over manner. Treatment settings were identical for individual patients: time 229 +/- 22 min; blood flow rate 378 +/- 33 mL/min; dialysate flow rate 500 mL/min; substitution flow rate in haemodiafiltration 94 +/- 9 mL/min. Removal of the protein-bound compounds p-cresyl sulfate (pCS) and indoxyl sulfate (IS) was determined by reduction ratios (RRs), dialytic clearances and mass in continuously collected dialysate. In addition, the elimination of the low-molecular weight (LMW) proteins beta(2)-microglobulin, cystatin c, myoglobin (myo), free retinol-binding protein (rbp) and albumin was measured.
  
  
  RESULTS
  Plasma levels of the protein-bound toxins were significantly decreased by all treatment forms. However, the decreases were comparable between dialysis membranes and between haemodialysis and haemodiafiltration. The RRs of total pCS ranged between 40.4 +/- 25.3 and 47.8 +/- 10.3% and of total IS between 50.4 +/- 2.6 and 54.6 +/- 8.7%. Elimination of free protein-bound toxins as assessed by their mass in dialysate closely correlated positively with the pre-treatment plasma concentrations being r = 0.920 (P < 0.001) for total pCS and r = 0.906 (P < 0.001) for total IS, respectively. Compared to haemodialysis, much higher removal of all LMW proteins was found in haemodiafiltration. Dialysis membrane differences were only obvious in haemodialysis for the larger LMW proteins myo and rbp yielding significantly higher RRs for PU+ (myo 46 +/- 9 versus 37 +/- 9%; rbp 18 +/- 5 versus 15 +/- 5%; P < 0.05). Additionally, the albumin loss varied between membranes and treatment modes being undetectable with PU- in haemodialysis and highest with PU+ in haemodiafiltration (1430 +/- 566 mg).
  
  
  CONCLUSIONS
  The elimination of protein-bound compounds into dialysate is predicted by the level of pre-treatment plasma concentrations and depends particularly on diffusion. Lacking enhanced removal in online post-dilution haemodiafiltration emphasizes the minor significance of convection for the clearance of these solutes. Compared to LMW proteins, the highly protein-bound toxins pCS and IS are less effectively eliminated with all treatment forms. For a sustained decrease of pCS and IS plasma levels, alternative strategies promise to be more efficient therapy forms.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany. krieter_d@medizin.uni-wuerzburg.de
authors.forename: Detlef H
authors.initials: DH
authors.lastname: Krieter
authors.forename: Andrea
authors.initials: A
authors.lastname: Hackl
authors.forename: Annie
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Leïla
authors.initials: L
authors.lastname: Chenine
authors.forename: Hélène Leray
authors.initials: HL
authors.lastname: Moragues
authors.forename: Horst-Dieter
authors.initials: HD
authors.lastname: Lemke
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Bernard
authors.initials: B
authors.lastname: Canaud
mesh_terms: D000368:Aged; D003408:Cresols / Q000097:blood*; D018592:Cross-Over Studies; D055316:Cystatin C / Q000097:blood; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D007200:Indican / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009211:Myoglobin / Q000097:blood; D011108:Polymers; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D012177:Retinol-Binding Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013450:Sulfones; D013463:Sulfuric Acid Esters / Q000097:blood*; D014511:Uremia / Q000097:blood / Q000628:therapy*; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D003408:Cresols; D055316:Cystatin C; D009211:Myoglobin; D011108:Polymers; D012177:Retinol-Binding Proteins; D012709:Serum Albumin; D013450:Sulfones; D013463:Sulfuric Acid Esters; D001613:beta 2-Microglobulin; C022840:polyether sulfone; C408690:4-cresol sulfate; D007200:Indican