title: Middle-molecule clearance at 20 and 35 ml/kg/h in continuous venovenous hemodiafiltration.
abstract: BACKGROUND
  Of 5 clinical trials testing dose response of continuous renal replacement therapy (CRRT) in acute kidney injury, 2 showed a benefit, 2 showed none, and 1 appeared equivocal. However, blood-membrane interactions may dominate macromolecule transport in continuous venovenous hemodiafiltration, reducing the impact of dose adjustment. The dosing arms in the Acute Renal Failure Trial Network (ATN) study may have delivered similar clearances for middle molecules.
  
  
  METHODS
  We simulated the 2 CRRT doses in the ATN study using a synthetic polydisperse macromolecular probe in bovine blood. Clearance of tracers between 10 and 100 kDa molecular weight was measured during 6 h of therapy.
  
  
  RESULTS
  Middle-molecule clearance differed by less than 2 ml/min between the 2 dosing arms.
  
  
  CONCLUSIONS
  The CRRT prescription used in the ATN study appears to have achieved dose separation for small molecules while holding middle-molecule clearance nearly constant. This may explain the outcome difference between the ATN study and earlier studies, and suggests subsequent trial designs.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Hofmann
authors.forename: W H
authors.initials: WH
authors.lastname: Fissell
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy*; D000818:Animals; D002417:Cattle; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017582:Renal Replacement Therapy / Q000379:methods; D014118:Toxins, Biological / Q000652:urine*
chemical_list: D014118:Toxins, Biological; C026865:uremia middle molecule toxins