title: Vitamin K Metabolism in a Rat Model of Chronic Kidney Disease.
abstract: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinone (K1). Menaquinone-4 (MK-4) is the form of vitamin K that is preferentially found in extra-hepatic tissues.
  
  
  
  In the present study, we assessed tissue concentrations of K1 and MK-4 and the expression of vitamin K-related genes in a rat model of adenine-induced CKD.
  
  
  
  It was found that rats with both mild and severe CKD had significantly lower amounts of K1 measured in liver, spleen and heart and higher levels of MK-4 measured in kidney cortex and medulla. All animals treated with high dietary K1 had an increase in tissue levels of both K1 and MK-4; however, the relative increase in K1 differed suggesting that the conversion of K1 to MK-4 may be a regulated/limiting process in some tissues. There was a decrease in the thoracic aorta expression of vitamin K recycling (Vkor) and utilization (Ggcx) enzymes, and a decrease in the kidney level of vitamin K1 to MK-4 bioconversion enzyme Ubiad1 in CKD.
  
  
  
  Taken together, these findings suggest that CKD impacts vitamin K metabolism, and this occurs early in the disease course. Our findings that vitamin K metabolism is altered in the presence of CKD provides further support that sub-clinical vitamin K deficiency may represent a modifiable risk factor for vascular and bone health in this population.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ont., Canada.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: McCabe
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.forename: Xueyan
authors.initials: X
authors.lastname: Fu
authors.forename: Emilie
authors.initials: E
authors.lastname: Ward
authors.forename: Michael A
authors.initials: MA
authors.lastname: Adams
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Holden
mesh_terms: D000225:Adenine / Q000633:toxicity; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D019735:Carbon-Carbon Ligases / Q000235:genetics / Q000378:metabolism; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism; D008297:Male; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D014812:Vitamin K / Q000378:metabolism*; D010837:Vitamin K 1 / Q000378:metabolism*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases / Q000235:genetics / Q000378:metabolism
chemical_list: D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D010837:Vitamin K 1; C578519:VKORC1 protein, rat; D064417:Vitamin K Epoxide Reductases; D004122:Dimethylallyltranstransferase; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D000225:Adenine