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

Abstract

The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease, with vascular calcification being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This γ-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, either by increasing dietary vitamin K intake or by antagonism with therapeutic doses of warfarin, could alter the development of vascular calcification in male Sprague-Dawley rats with adenine-induced CKD. Treatment of CKD rats with warfarin markedly increased pulse pressure and pulse wave velocity, as well as significantly increased calcium concentrations 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) and blunted the development of vascular calcification. Thus, vitamin K has an important role in modifying mechanisms linked to the susceptibility of arteries to calcify in an experimental model of CKD.

• Authors: Kristin M McCabe, Sarah L Booth, Xueyan Fu, Navid Shobeiri, Judith J Pang, Michael A Adams, Rachel M Holden
• Journal: Kidney international (Kidney Int) Vol. 83 Issue 5 Pg. 835-44 (May 2013) ISSN: 1523-1755 [Electronic] United States
• PMID: 23344475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Biomarkers
• Osteocalcin
• Vitamin K 2
• menatetrenone
• Warfarin
• Vitamin K 1
• Adenine

Topics

• Adenine
• Animals
• Anticoagulants (toxicity)
• Arteries (drug effects, metabolism, pathology, physiopathology)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• Dietary Supplements
• Disease Models, Animal
• Disease Progression
• Male
• Osteocalcin (blood)
• Pulse Wave Analysis
• Rats
• Rats, Sprague-Dawley
• Renal Insufficiency, Chronic (blood, chemically induced, drug therapy, pathology, physiopathology)
• Time Factors
• Vascular Calcification (blood, chemically induced, pathology, physiopathology, prevention & control)
• Vitamin K 1 (metabolism, pharmacology)
• Vitamin K 2 (analogs & derivatives, metabolism)
• Warfarin (toxicity)