title: Relative abundance of fetuin- A in peritoneal dialysis effluent and its association with in situ formation of calciprotein particles: an observational pilot study.
abstract: OBJECTIVE
  In patients with renal failure or chronic inflammation, the accumulation of fetuin-A-containing calciprotein particles (CPP) in the extracellular fluid has been implicated in driving inflammatory pathways and extraosseous mineral deposition. We aimed to discover whether CPP are present in the peritoneal dialysis fluid effluent (PDF) of stable peritoneal dialysis (PD) patients, and if so, how these particles might be formed.
  
  
  METHODS
  Serum and PDF were sampled from 20 stable PD patients. CPP were quantified by the reduction in fetuin-A concentration after high speed centrifugation. 8-iso-PGF2α in PDF was measured as a marker of oxidative stress. Fetuin-A and phosphate were added to commercially available dialysis fluids to assess their ability to support CPP formation ex vivo.
  
  
  RESULTS
  We report that the major protein component of these mineral-containing nanoparticles, fetuin-A, is relatively abundant in PDF and that CPP were present in the PDF of 17/20 PD patients. PDF CPP levels were strongly correlated with 8-iso-PGF2α concentrations. In vitro experiments suggested that commonly used peritoneal dialysate fluids, irrespective of composition, could not sustain appreciable de novo CPP formation ex vivo.
  
  
  CONCLUSIONS
  Fetuin-A is either actively transported or locally produced by the peritoneal membrane in PD patients. The association between fetuin-A-containing CPP and markers of oxidative stress warrants further mechanistic studies.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Michael Mx
authors.initials: MM
authors.lastname: Cai
authors.forename: Belinda
authors.initials: B
authors.lastname: Wigg
authors.forename: Edward R
authors.initials: ER
authors.lastname: Smith
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Hewitson
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: McMahon
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holt
mesh_terms: D015415:Biomarkers / Q000032:analysis; D059587:Calcifying Nanoparticles / Q000096:biosynthesis*; D015314:Dialysis Solutions / Q000737:chemistry*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D010530:Peritoneal Dialysis; D010865:Pilot Projects; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis*
chemical_list: D015415:Biomarkers; D059587:Calcifying Nanoparticles; D015314:Dialysis Solutions; D060749:alpha-2-HS-Glycoprotein; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost
keywords: fetuin-A; inflammation; oxidative stress; peritoneal dialysis; renal failure