The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population

Abstract Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, u...

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Autores principales:	Arnold Piek, Leonie Smit, Navin Suthahar, Stephan J. L. Bakker, Rudolf A. de Boer, Herman H. W. Silljé
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de60494287fb41dbba247de069f29ab7
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spelling	oai:doaj.org-article:de60494287fb41dbba247de069f29ab72021-12-02T18:27:46ZThe emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population10.1038/s41598-021-88107-92045-2322https://doaj.org/article/de60494287fb41dbba247de069f29ab72021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88107-9https://doaj.org/toc/2045-2322Abstract Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, using enzyme-linked immunosorbent assays. Associations with clinical variables and outcomes were analysed. Median DKK3 level was 32.8 ng/ml (28.0–39.0). In multivariable linear regression analysis, the strongest correlates for plasma DKK3 were age, body mass index and estimated glomerular filtration rate (eGFR). At baseline, 564 (6.7%) subjects had CVD (defined as a myocardial infarction and/or cerebrovascular accident) and 1361 (16.2%) subjects had CKD (defined as eGFR < 60 ml/min/1.73m2 and/or urinary albumin excretion (UAE) > 30 mg/24 h). Of subjects with known CVD and CKD follow-up status (respectively 7828 and 5548), 669 (8.5%) developed CVD and 951 (17.1%) developed CKD (median follow-up respectively 12.5 and 10.2 years). Crude logistic regression analysis revealed that DKK3 levels were associated with prevalent CVD (Odds ratio: 2.14 [1.76–2.61] per DKK3 doubling, P < 0.001) and CKD (Odds ratio: 1.84 [1.59–2.13] per DKK3 doubling, P < 0.001). In crude Cox proportional hazard regression analysis, higher DKK3 levels were associated with higher risk for new-onset CVD (Hazard ratio: 1.47 [1.13–1.91] per DKK3 doubling, P = 0.004) and CKD (Hazard ratio: 1.45, [1.25–1.69] per DKK3 doubling, P < 0.001). However, these associations remained no longer significant after correction for common clinical variables and risk factors, though independently predicted for new-onset CKD in a subgroup of subjects with the lowest UAE values. Together, DKK3 plasma levels are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD and only predicted for new-onset CKD in those subjects with the lowest UAE values.Arnold PiekLeonie SmitNavin SuthaharStephan J. L. BakkerRudolf A. de BoerHerman H. W. SilljéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arnold Piek Leonie Smit Navin Suthahar Stephan J. L. Bakker Rudolf A. de Boer Herman H. W. Silljé The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
description	Abstract Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, using enzyme-linked immunosorbent assays. Associations with clinical variables and outcomes were analysed. Median DKK3 level was 32.8 ng/ml (28.0–39.0). In multivariable linear regression analysis, the strongest correlates for plasma DKK3 were age, body mass index and estimated glomerular filtration rate (eGFR). At baseline, 564 (6.7%) subjects had CVD (defined as a myocardial infarction and/or cerebrovascular accident) and 1361 (16.2%) subjects had CKD (defined as eGFR < 60 ml/min/1.73m2 and/or urinary albumin excretion (UAE) > 30 mg/24 h). Of subjects with known CVD and CKD follow-up status (respectively 7828 and 5548), 669 (8.5%) developed CVD and 951 (17.1%) developed CKD (median follow-up respectively 12.5 and 10.2 years). Crude logistic regression analysis revealed that DKK3 levels were associated with prevalent CVD (Odds ratio: 2.14 [1.76–2.61] per DKK3 doubling, P < 0.001) and CKD (Odds ratio: 1.84 [1.59–2.13] per DKK3 doubling, P < 0.001). In crude Cox proportional hazard regression analysis, higher DKK3 levels were associated with higher risk for new-onset CVD (Hazard ratio: 1.47 [1.13–1.91] per DKK3 doubling, P = 0.004) and CKD (Hazard ratio: 1.45, [1.25–1.69] per DKK3 doubling, P < 0.001). However, these associations remained no longer significant after correction for common clinical variables and risk factors, though independently predicted for new-onset CKD in a subgroup of subjects with the lowest UAE values. Together, DKK3 plasma levels are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD and only predicted for new-onset CKD in those subjects with the lowest UAE values.
format	article
author	Arnold Piek Leonie Smit Navin Suthahar Stephan J. L. Bakker Rudolf A. de Boer Herman H. W. Silljé
author_facet	Arnold Piek Leonie Smit Navin Suthahar Stephan J. L. Bakker Rudolf A. de Boer Herman H. W. Silljé
author_sort	Arnold Piek
title	The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
title_short	The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
title_full	The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
title_fullStr	The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
title_full_unstemmed	The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population
title_sort	emerging plasma biomarker dickkopf-3 (dkk3) and its association with renal and cardiovascular disease in the general population
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de60494287fb41dbba247de069f29ab7
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The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population

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