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.