Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease

Abstract Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However...

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Autores principales:	Javier Donate-Correa, Carla M. Ferri, Ernesto Martín-Núñez, Nayra Pérez-Delgado, Ainhoa González-Luis, Carmen Mora-Fernández, Juan F. Navarro-González
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9ea4b5ddcc44e2f8897e955395cf614
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spelling	oai:doaj.org-article:a9ea4b5ddcc44e2f8897e955395cf6142021-12-02T16:35:46ZKlotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease10.1038/s41598-021-95488-42045-2322https://doaj.org/article/a9ea4b5ddcc44e2f8897e955395cf6142021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95488-4https://doaj.org/toc/2045-2322Abstract Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs) are also associated with subclinical atherosclerosis in CKD. The present study aimed to study the relationship between Klotho and subclinical atherosclerosis in a population of patients with moderate to severe CKD. We determined the serum levels and gene expression in PBCs levels of Klotho and three inflammatory cytokines in 103 patients with CKD and investigated their relationship with two surrogate markers of subclinical atherosclerotis: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Patients with subclinical atherosclerosis presented lower serum and PBCs expression levels of Klotho. Both variables were associated with the presence of subclinical atherosclerosis, being directly related with ABI and inversely with CIMT (P < 0.0001 for both). Multiple regression analysis demonstrated that both variables were significant determinants for ABI (adjusted R2 = 0.511, P < 0.0001) and CIMT (adjusted R2 = 0.445, P < 0.0001), independently of traditional and emergent cardiovascular risk factors. Moreover, both constituted protective factors against subclinical atherosclerosis [OR: 0.993 (P = 0.002) and 0.231 (P = 0.025), respectively]. Receiver operating characteristic analysis pointed to the utility of serum Klotho (area under the curve [AUC]: 0.817, 95% CI: 0.736–0.898, P < 0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: 0.647–0.836, P < 0.001) to distinguish subclinical atherosclerosis. The reductions in serum and PBCs expression levels of Klotho in CKD patients are independently associated with the presence of for subclinical atherosclerosis. Further research exploring whether therapeutic approaches to maintain or elevate Klotho could reduce the impact of CVD in CKD patients is warranted.Javier Donate-CorreaCarla M. FerriErnesto Martín-NúñezNayra Pérez-DelgadoAinhoa González-LuisCarmen Mora-FernándezJuan F. Navarro-GonzálezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Javier Donate-Correa Carla M. Ferri Ernesto Martín-Núñez Nayra Pérez-Delgado Ainhoa González-Luis Carmen Mora-Fernández Juan F. Navarro-González Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
description	Abstract Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs) are also associated with subclinical atherosclerosis in CKD. The present study aimed to study the relationship between Klotho and subclinical atherosclerosis in a population of patients with moderate to severe CKD. We determined the serum levels and gene expression in PBCs levels of Klotho and three inflammatory cytokines in 103 patients with CKD and investigated their relationship with two surrogate markers of subclinical atherosclerotis: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Patients with subclinical atherosclerosis presented lower serum and PBCs expression levels of Klotho. Both variables were associated with the presence of subclinical atherosclerosis, being directly related with ABI and inversely with CIMT (P < 0.0001 for both). Multiple regression analysis demonstrated that both variables were significant determinants for ABI (adjusted R2 = 0.511, P < 0.0001) and CIMT (adjusted R2 = 0.445, P < 0.0001), independently of traditional and emergent cardiovascular risk factors. Moreover, both constituted protective factors against subclinical atherosclerosis [OR: 0.993 (P = 0.002) and 0.231 (P = 0.025), respectively]. Receiver operating characteristic analysis pointed to the utility of serum Klotho (area under the curve [AUC]: 0.817, 95% CI: 0.736–0.898, P < 0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: 0.647–0.836, P < 0.001) to distinguish subclinical atherosclerosis. The reductions in serum and PBCs expression levels of Klotho in CKD patients are independently associated with the presence of for subclinical atherosclerosis. Further research exploring whether therapeutic approaches to maintain or elevate Klotho could reduce the impact of CVD in CKD patients is warranted.
format	article
author	Javier Donate-Correa Carla M. Ferri Ernesto Martín-Núñez Nayra Pérez-Delgado Ainhoa González-Luis Carmen Mora-Fernández Juan F. Navarro-González
author_facet	Javier Donate-Correa Carla M. Ferri Ernesto Martín-Núñez Nayra Pérez-Delgado Ainhoa González-Luis Carmen Mora-Fernández Juan F. Navarro-González
author_sort	Javier Donate-Correa
title	Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
title_short	Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
title_full	Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
title_fullStr	Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
title_full_unstemmed	Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
title_sort	klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a9ea4b5ddcc44e2f8897e955395cf614
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Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease

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