Page Banner

United States Department of Agriculture

Agricultural Research Service

Research Project: VITAMIN K: FOOD COMPOSITION, BIOAVAILABILITY AND IT'S ROLE IN HUMAN HEALTH

Location: Human Nutrition Research Center on Aging

Title: Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

Authors
item Kristin, Mccabe -
item Sarah, Booth -
item Xueyan, Fu -
item Shobeiri, Navid -
item Pang, Judy -
item Adams, Michael -
item Holden, Rachel -

Submitted to: Kidney International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 8, 2012
Publication Date: May 1, 2013
Citation: Kristin, M.M., Sarah, B.L., Xueyan, F., Shobeiri, N., Pang, J., Adams, M.A., Holden, R.M. 2013. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease. Kidney International. 83:835-844.

Interpretive Summary: The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD). The progression of calcification in the vessels is a key determinant of the progression of CVD in these patients. A local regulator of vascular calcification is vitamin K. Vitamin K is required for the activation of several proteins that inhibit calcification. Warfarin, a common therapy in CKD patients, inhibits the function of vitamin K and thereby decreases the inhibitory activity of these vitamin K-dependent proteins. In this study we sought to determine whether modifying vitamin K status either by increasing dietary vitamin K intake or by antagonism with warfarin could alter the development of vascular calcification in male Sprague Dawley rats with experimentally-induced CKD. Treatment of CKD rats with warfarin markedly increased levels of calcium in the thoracic aorta (3 fold), abdominal aorta (8 fold), renal artery (4 fold) and carotid artery (20 fold). In contrast, treatment with high dietary vitamin K increased vitamin K tissue concentrations (10-300 fold increase) and blunted the development of vascular calcification. The findings clearly demonstrate that vitamin K status plays an important role in modifying mechanisms linked to the susceptibility of arteries to calcification in an experimental model of CKD. Vitamin K status appears to be a modifiable risk factor for CVD in CKD.

Technical Abstract: The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential cofactor in the activation of several extracellular matrix proteins that inhibit calcification. Warfarin, a common therapy in dialysis patients, inhibits the recycling of vitamin K and thereby decreases the inhibitory activity of these proteins. In this study we sought to determine whether modifying vitamin K status (vitamin K1 0.1-0.2 mg/kg diet), either by increasing dietary vitamin K intake (high vitamin K1, 100 mg/kg diet) or by antagonism with therapeutic doses of warfarin (0.08-0.1 mg/kg body weight/day) could alter the development of VC in male Sprague Dawley rats with adenine-induced CKD (0.25% in diet). Treatment of CKD rats with warfarin markedly increased pulse pressure (50% increase) and pulse wave velocity (2 fold elevation), as well as significantly increased levels of calcium in the thoracic aorta (3 fold),abdominal aorta (8 fold), renal artery (4 fold) and carotid artery (20 fold). In contrast, treatment with high dietary vitamin K1 increased vitamin K tissue concentrations (10-300 fold increase) and blunted the development of VC. The findings clearly demonstrate that vitamin K status plays an important role in modifying mechanisms linked to the susceptibility of arteries to calcification in an experimental model of CKD. Vitamin K status appears to be a modifiable risk factor for CVD in CKD.

Last Modified: 9/10/2014
Footer Content Back to Top of Page