Relative abundance of fetuin- A in peritoneal dialysis effluent and its association with in situ formation of calciprotein particles: An observational pilot study

• Published in: Nephrology (Carlton, Vic.) Vic.), 2015-01, Vol.20 (1), p.6-10
• Main Authors: Cai, Michael MX, Wigg, Belinda, Smith, Edward R, Hewitson, Timothy D, McMahon, Lawrence P, Holt, Stephen G
• Format: Article
• Language: English
• Subjects: alpha-2-HS-Glycoprotein - analysis; Biomarkers - analysis; Calcifying Nanoparticles - biosynthesis; Dialysis Solutions - chemistry; Dinoprost - analogs & derivatives; Dinoprost - analysis; fetuin-A; Humans; inflammation; oxidative stress; Peritoneal Dialysis; Pilot Projects; renal failure
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/nep.12350

Aim 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. Conclusion 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. Summary at a Glance Oxidative stress, infection and glycation end products affect peritoneal membrane integrity. In this study, calciprotein particles (CPPs), formed from fetuin‐A and calcium‐phosphate crystals, were found in peritoneal dialysis fluid and were associated with an oxidative stress marker. Further studies need to determine how CPPs accumulate and whether they initiate oxidative damage.