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Vitamin K, Vascular Calcification, and Chronic Kidney Disease: Current Evidence and Unanswered Questions.

ABSTRACT: More than 15% of the US population is currently >65 y old. As populations age there is a concomitant increase in age-related chronic diseases. One such disease is chronic kidney disease (CKD), which becomes more prevalent with age, especially over age 70 y. Individuals with CKD are at increased risk of cardiovascular disease, in part because arterial calcification increases as kidney function declines. Vitamin K is a shortfall nutrient among older adults that has been implicated in arterial calcification. Evidence suggests CKD patients have low vitamin K status, but data are equivocal because the biomarkers of vitamin K status can be influenced by CKD. Animal studies provide more compelling data on the underlying role of vitamin K in arterial calcification associated with CKD. The purpose of this review is to evaluate the strengths and limitations of the available evidence regarding the role of vitamin K in CKD.

SUBMITTER: Shea MK

PROVIDER: S-EPMC6775440 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Vitamin K, Vascular Calcification, and Chronic Kidney Disease: Current Evidence and Unanswered Questions.

Shea M Kyla MK Booth Sarah L SL

Current developments in nutrition 20190704 9

More than 15% of the US population is currently >65 y old. As populations age there is a concomitant increase in age-related chronic diseases. One such disease is chronic kidney disease (CKD), which becomes more prevalent with age, especially over age 70 y. Individuals with CKD are at increased risk of cardiovascular disease, in part because arterial calcification increases as kidney function declines. Vitamin K is a shortfall nutrient among older adults that has been implicated in arterial calc ...[more]

PMID: 31598579

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Project description:An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD-induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age-matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross-talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dataset Information

Vitamin K, Vascular Calcification, and Chronic Kidney Disease: Current Evidence and Unanswered Questions.

Publications

Vitamin K, Vascular Calcification, and Chronic Kidney Disease: Current Evidence and Unanswered Questions.

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