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

Kidney Int. 2013 May;83(5):835-44. doi: 10.1038/ki.2012.477. Epub 2013 Jan 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Animals
  • Anticoagulants / toxicity*
  • Arteries / drug effects*
  • Arteries / metabolism
  • Arteries / pathology
  • Arteries / 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
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / pathology
  • Renal Insufficiency, Chronic / physiopathology
  • Time Factors
  • Vascular Calcification / blood
  • Vascular Calcification / chemically induced*
  • Vascular Calcification / pathology
  • Vascular Calcification / physiopathology
  • Vascular Calcification / prevention & control*
  • Vitamin K 1 / metabolism
  • Vitamin K 1 / pharmacology*
  • Vitamin K 2 / analogs & derivatives
  • Vitamin K 2 / metabolism
  • Warfarin / toxicity*


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