New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis

Glorieux, G. et al. (2015) New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis. Nephrology Dialysis Transplantation, 30(11), pp. 1842-1852. (doi: 10.1093/ndt/gfv254) (PMID:26160894)

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BACKGROUND: The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation of uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least in part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on the role of individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight. METHODS: In a discovery study, we analysed the plasma proteome of patients with stage 2-3 CKD (n = 14) and stage 5 CKD with haemodialysis (HD) (n = 15), using high-resolution LC-MS/MS analysis. Selected results were validated in a cohort of 40 patients with different CKD stages with or without HD, using ELISA. RESULTS: Of a total of 2054 detected proteins, 127 displayed lower, while 206 displayed higher abundance in the plasma of patients on HD. Molecular pathway analysis confirmed the modification of known processes involved in CKD complications, including decreased haemostasis and increased inflammation, complement activation and vascular damage. In addition, we identified the plasma increase during CKD progression of lysozyme C and leucine-rich alpha-2 glycoprotein, two proteins related to vascular damage and heart failure. High level of leucine-rich alpha-2 glycoprotein was associated with higher mortality in stage 5 CKD patients on HD. CONCLUSIONS: This study provides for the first time a comprehensive assessment of CKD plasma proteome, contributing to new knowledge and potential markers of CKD. These results will serve as a basis for future studies investigating the relevance of these molecules in CKD associated morbidity and mortality.

Item Type:Articles (Other)
Glasgow Author(s) Enlighten ID:Mullen, Dr Bill and Husi, Dr Holger and Mischak, Professor Harald
Authors: Glorieux, G., Mullen, W., Duranton, F., Filip, S., Gayrard, N., Husi, H., Schepers, E., Neirynck, N., Schanstra, J. P., Jankowski, J., Mischak, H., Argilés, À., Vanholder, R., Vlahou, A., and Klein, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Nephrology Dialysis Transplantation
Journal Abbr.:NDT
Publisher:Oxford University Press
ISSN (Online):1460-2385
Published Online:09 July 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Nephrology Dialysis Transplantation 30(11): 1842-1852
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
637441IMODE-CKD: Clinical and system-omics for the identification of the Molecular Determinants of established Chronic Kidney DiseaseHolger HusiEuropean Commission (EC)608332RI CARDIOVASCULAR & MEDICAL SCIENCES
593511SysVascChristian DellesEuropean Commission (EC)603288RI CARDIOVASCULAR & MEDICAL SCIENCES