du.sePublications
4243444546474845 of 75
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • chicago-author-date
  • chicago-note-bibliography
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease.
Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska Institutet; Uppsala universitet.
Show others and affiliations
2018 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.

Place, publisher, year, edition, pages
2018.
Keywords [en]
CVD, ESRD, Proteomics
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-29000DOI: 10.1007/s40620-018-0556-5PubMedID: 30499038OAI: oai:DiVA.org:du-29000DiVA, id: diva2:1267695
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2018-12-03

Open Access in DiVA

fulltext(1126 kB)17 downloads
File information
File name FULLTEXT01.pdfFile size 1126 kBChecksum SHA-512
d60320bbcb9516646fc63a4d2f59ed905a135ddc1ec216cd35a9a71c6da4daeb11ec7ec8d0568384cda29afae28925a4a0286c11c8d472b65d6d8ff83e734916
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Rudholm Feldreich, TobiasÄrnlöv, Johan

Search in DiVA

By author/editor
Rudholm Feldreich, TobiasÄrnlöv, Johan
By organisation
Medical Science
In the same journal
JN. Journal of Nephrology (Milano. 1992)
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 17 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 12 hits
4243444546474845 of 75
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • chicago-author-date
  • chicago-note-bibliography
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf