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Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease

INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex...

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Autores principales: Feldreich, Tobias, Nowak, Christoph, Fall, Tove, Carlsson, Axel C., Carrero, Juan-Jesus, Ripsweden, Jonas, Qureshi, Abdul Rashid, Heimbürger, Olof, Barany, Peter, Stenvinkel, Peter, Vuilleumier, Nicolas, Kalra, Philip A., Green, Darren, Ärnlöv, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373380/
https://www.ncbi.nlm.nih.gov/pubmed/30499038
http://dx.doi.org/10.1007/s40620-018-0556-5
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author Feldreich, Tobias
Nowak, Christoph
Fall, Tove
Carlsson, Axel C.
Carrero, Juan-Jesus
Ripsweden, Jonas
Qureshi, Abdul Rashid
Heimbürger, Olof
Barany, Peter
Stenvinkel, Peter
Vuilleumier, Nicolas
Kalra, Philip A.
Green, Darren
Ärnlöv, Johan
author_facet Feldreich, Tobias
Nowak, Christoph
Fall, Tove
Carlsson, Axel C.
Carrero, Juan-Jesus
Ripsweden, Jonas
Qureshi, Abdul Rashid
Heimbürger, Olof
Barany, Peter
Stenvinkel, Peter
Vuilleumier, Nicolas
Kalra, Philip A.
Green, Darren
Ärnlöv, Johan
author_sort Feldreich, Tobias
collection PubMed
description INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). RESULTS: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort. CONCLUSIONS: Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40620-018-0556-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-63733802019-03-01 Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease Feldreich, Tobias Nowak, Christoph Fall, Tove Carlsson, Axel C. Carrero, Juan-Jesus Ripsweden, Jonas Qureshi, Abdul Rashid Heimbürger, Olof Barany, Peter Stenvinkel, Peter Vuilleumier, Nicolas Kalra, Philip A. Green, Darren Ärnlöv, Johan J Nephrol Original Article INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). RESULTS: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort. CONCLUSIONS: Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40620-018-0556-5) contains supplementary material, which is available to authorized users. Springer International Publishing 2018-11-29 2019 /pmc/articles/PMC6373380/ /pubmed/30499038 http://dx.doi.org/10.1007/s40620-018-0556-5 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Feldreich, Tobias
Nowak, Christoph
Fall, Tove
Carlsson, Axel C.
Carrero, Juan-Jesus
Ripsweden, Jonas
Qureshi, Abdul Rashid
Heimbürger, Olof
Barany, Peter
Stenvinkel, Peter
Vuilleumier, Nicolas
Kalra, Philip A.
Green, Darren
Ärnlöv, Johan
Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title_full Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title_fullStr Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title_full_unstemmed Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title_short Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
title_sort circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373380/
https://www.ncbi.nlm.nih.gov/pubmed/30499038
http://dx.doi.org/10.1007/s40620-018-0556-5
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