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

Lambie; Davies

Abstract

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 ?-chain and heparan sulphate proteoglycan core protein progressively
increased over time on PD. In patients who developed EPS, collagen-a1(I), ?-actin and Complement
factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HSglycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and
a1-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.

Citation

Lambie, & Davies. (2017). A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent. Kidney International, 988-1002. https://doi.org/10.1016/j.kint.2017.03.030

• Acceptance Date: Mar 16, 2017
• Publication Date: Oct 1, 2017
• Journal: Kidney International
• Print ISSN: 0085-2538
• Publisher: Elsevier
• Pages: 988-1002
• DOI: https://doi.org/10.1016/j.kint.2017.03.030
• Keywords: peritoneal dialysis, proteomic analysis, peritoneal membrane
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0085253817302338?dgcid=raven_sd_aip_email