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

(2015) NEPHROLOGY DIALYSIS TRANSPLANTATION. 30(11). p.1842-1852
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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
haemodialysis, mechanisms, chronic kidney disease, biomarkers, proteomics, uraemic solutes, GLYCATION END-PRODUCTS, INFLAMMATORY MARKERS, COAGULATION-FACTORS, ARTERIAL-DISEASE, SYSTEMS BIOLOGY, UREMIC TOXINS, BIOMARKER, HEMODIALYSIS, LYSOZYME, ATHEROSCLEROSIS

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MLA
Glorieux, Griet et al. “New Insights in Molecular Mechanisms Involved in Chronic Kidney Disease Using High-resolution Plasma Proteome Analysis.” NEPHROLOGY DIALYSIS TRANSPLANTATION 30.11 (2015): 1842–1852. Print.
APA
Glorieux, G., Mullen, W., Duranton, F., Filip, S., Gayrard, N., Husi, H., Schepers, E., et al. (2015). New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis. NEPHROLOGY DIALYSIS TRANSPLANTATION, 30(11), 1842–1852.
Chicago author-date
Glorieux, Griet, William Mullen, Flore Duranton, Szymon Filip, Nathalie Gayrard, Holger Husi, Eva Schepers, et al. 2015. “New Insights in Molecular Mechanisms Involved in Chronic Kidney Disease Using High-resolution Plasma Proteome Analysis.” Nephrology Dialysis Transplantation 30 (11): 1842–1852.
Chicago author-date (all authors)
Glorieux, Griet, William Mullen, Flore Duranton, Szymon Filip, Nathalie Gayrard, Holger Husi, Eva Schepers, Nathalie Neirynck, Joost P Schanstra, Joachim Jankowski, Harald Mischak, Ángel Argilés, Raymond Vanholder, Antonia Vlahou, and Julie Klein. 2015. “New Insights in Molecular Mechanisms Involved in Chronic Kidney Disease Using High-resolution Plasma Proteome Analysis.” Nephrology Dialysis Transplantation 30 (11): 1842–1852.
Vancouver
1.
Glorieux G, Mullen W, Duranton F, Filip S, Gayrard N, Husi H, et al. New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis. NEPHROLOGY DIALYSIS TRANSPLANTATION. 2015;30(11):1842–52.
IEEE
[1]
G. Glorieux et al., “New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis,” NEPHROLOGY DIALYSIS TRANSPLANTATION, vol. 30, no. 11, pp. 1842–1852, 2015.
@article{7095078,
  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.},
  author       = {Glorieux, Griet and Mullen, William and Duranton, Flore and Filip, Szymon and Gayrard, Nathalie and Husi, Holger and Schepers, Eva and Neirynck, Nathalie and Schanstra, Joost P and Jankowski, Joachim and Mischak, Harald and Argilés, Ángel and Vanholder, Raymond and Vlahou, Antonia and Klein, Julie},
  issn         = {0931-0509},
  journal      = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
  keywords     = {haemodialysis,mechanisms,chronic kidney disease,biomarkers,proteomics,uraemic solutes,GLYCATION END-PRODUCTS,INFLAMMATORY MARKERS,COAGULATION-FACTORS,ARTERIAL-DISEASE,SYSTEMS BIOLOGY,UREMIC TOXINS,BIOMARKER,HEMODIALYSIS,LYSOZYME,ATHEROSCLEROSIS},
  language     = {eng},
  number       = {11},
  pages        = {1842--1852},
  title        = {New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis},
  url          = {http://dx.doi.org/10.1093/ndt/gfv254},
  volume       = {30},
  year         = {2015},
}

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