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Nephrol Dial Transplant. 2015 Nov;30(11):1842-52. doi: 10.1093/ndt/gfv254. Epub 2015 Jul 9.

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

Author information

1
Nephrology Section, Ghent University Hospital, Gent, Belgium.
2
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
3
RD Néphrologie, Montpellier, France.
4
Biomedical Research Foundation, Academy of Athens, Athens, Greece Charité - Universitätsmedizin Berlin, Berlin, Germany.
5
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France Université Toulouse III Paul-Sabatier, Toulouse, France.
6
University Hospital RWTH, Institute for Molecular Cardiovascular Research, Aachen, Germany.
7
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK Mosaiques Diagnostics, Hannover, Germany.
8
Biomedical Research Foundation, Academy of Athens, Athens, Greece School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.

Abstract

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.

KEYWORDS:

biomarkers; chronic kidney disease; haemodialysis; mechanisms; proteomics; uraemic solutes

PMID:
26160894
DOI:
10.1093/ndt/gfv254
[Indexed for MEDLINE]

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