title: Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood.
abstract: BACKGROUND
  The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.
  
  
  METHODS
  The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.
  
  
  RESULTS
  Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.
  
  
  CONCLUSIONS
  Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.
authors.affiliation: Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sandholm
authors.affiliation: Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden ; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3 , Uppsala University , Uppsala , Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Jonsson
authors.affiliation: Gambro Lundia AB , Lund , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: Gambro Lundia AB , Lund , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wieslander
authors.affiliation: Gambro Lundia AB , Lund , Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Grundström
authors.affiliation: Gambro Lundia AB , Lund , Sweden.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Hancock
authors.affiliation: Linnæus Center for Biomaterials Chemistry , Linnæus University , Kalmar , Sweden ; Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3 , Uppsala University , Uppsala , Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
keywords: acetate; biocompatibility; citrate; complement; haemodialysis