title: New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis.
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.
authors.affiliation: Nephrology Section, Ghent University Hospital, Gent, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: RD Néphrologie, Montpellier, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Duranton
authors.affiliation: Biomedical Research Foundation, Academy of Athens, Athens, Greece Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Szymon
authors.initials: S
authors.lastname: Filip
authors.affiliation: RD Néphrologie, Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gayrard
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.affiliation: Nephrology Section, Ghent University Hospital, Gent, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Schepers
authors.affiliation: Nephrology Section, Ghent University Hospital, Gent, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Neirynck
authors.affiliation: 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.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: University Hospital RWTH, Institute for Molecular Cardiovascular Research, Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK Mosaiques Diagnostics, Hannover, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: RD Néphrologie, Montpellier, France.
authors.forename: Àngel
authors.initials: À
authors.lastname: Argilés
authors.affiliation: Nephrology Section, Ghent University Hospital, Gent, Belgium.
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.affiliation: Biomedical Research Foundation, Academy of Athens, Athens, Greece School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: biomarkers; chronic kidney disease; haemodialysis; mechanisms; proteomics; uraemic solutes