A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent

Vasileios Zavvos, Anthony T Buxton, Caroline Evans, Mark Lambie, Simon J Davies, Nicholas Topley, Martin Wilkie, Angela Summers, Paul Brenchley, Dimitrios S Goumenos, Timothy S Johnson

Research output: Contribution to journalArticlepeer-review


Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. We therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the diagnosis of EPS and would be valuable in stratifying at-risk patients and driving appropriate interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We employed a combinatorial peptide ligand library to compress the dynamic range of protein concentrations to aid identification of low-abundance proteins. In patients with stable membrane function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HS-glycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an increased number of proteins detected with improved resolution of protein spots, compared to the full fluid proteome. Intelectin-1, dermatopontin, gelsolin, and retinol binding protein-4 were elevated in proteome-mined samples from patients with EPS compared to patients that had just commenced peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.

Original languageEnglish
Pages (from-to)988-1002
Number of pages15
JournalKidney International
Issue number4
Early online date1 Jul 2017
Publication statusPublished - Oct 2017


  • Adult
  • Aged
  • Biomarkers/analysis
  • Dialysis Solutions/chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Kidney Failure, Chronic/therapy
  • Male
  • Middle Aged
  • Peritoneal Dialysis/adverse effects
  • Peritoneal Fibrosis/diagnosis
  • Peritoneum/pathology
  • Prognosis
  • Prospective Studies
  • Proteome/analysis
  • Proteomics/methods
  • Risk Assessment/methods


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