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Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol, Care Sci & Soc, Karlskrona, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.ORCID iD: 0000-0003-2247-8454
Karolinska Inst, Div Renal Med, Dept Clin Sci, Intervent & Technol, Karlskrona, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2017 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, no 4, 340-348 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

Place, publisher, year, edition, pages
2017. no 4, 340-348 p.
Keyword [en]
Kidney pathology, T-cell immunoglobulin mucin, kidney injury molecule 1, kallikrein-11, placenta growth factor, growth/differentiation, factor-15, macrophage inhibitory cytokine-1, urokinase plasminogen activator surface receptor
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:uu:diva-306601DOI: 10.1177/2047487316676134ISI: 000397434200003PubMedID: 27794105OAI: oai:DiVA.org:uu-306601DiVA: diva2:1040878
Funder
Swedish Research CouncilSwedish Heart Lung FoundationEU, Horizon 2020, 634869Marianne and Marcus Wallenberg Foundation
Available from: 2016-10-30 Created: 2016-10-30 Last updated: 2017-04-19Bibliographically approved

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Carlsson, Axel C.Sundström, JohanGustafsson, StefanStenemo, MarkusLarsson, AndersLind, LarsÄrnlöv, Johan
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Cardiovascular epidemiologyDepartment of Medical SciencesUCR-Uppsala Clinical Research CenterMolecular epidemiologyBiochemial structure and function
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Public Health, Global Health, Social Medicine and Epidemiology

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