Impaired vitamin K recycling in uremia is rescued by vitamin K supplementation.

Abstract

In chronic kidney disease, vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein, are largely uncarboxylated indicating that functional vitamin K deficiency may contribute to uremic vascular calcification. Since the effects of uremia on the vitamin K cycle are unknown, we investigated the influence of uremia and vitamin K supplementation on the activity of the vitamin K cycle and extraosseous calcification. Uremia was induced in rats by an adenine-supplemented diet and vitamin K1 or K2 was administered over 4 and 7 weeks. After 4 weeks of adenine diet, the activity of the vitamin K cycle enzyme γ-carboxylase but not the activities of DT-diaphorase or vitamin K epoxide reductase were reduced. Serum levels of undercarboxylated matrix Gla protein increased, indicating functional vitamin K deficiency. There was no light microscopy-detectable calcification at this stage but chemically determined aortic and renal calcium content was increased. Vitamin K treatment reduced aortic and renal calcium content after 4 weeks. Seven weeks of uremia induced overt calcification in the aorta, heart, and kidneys; however, addition of vitamin K restored intrarenal γ-carboxylase activity and overstimulated it in the liver along with reducing heart and kidney calcification. Thus, uremic vitamin K deficiency may partially result from a reduction of the γ-carboxylase activity which possibly contributes to calcification. Pharmacological vitamin K supplementation restored the vitamin K cycle and slowed development of soft tissue calcification in experimental uremia.

• Authors: Nadine Kaesler, Elke Magdeleyns, Marjolein Herfs, Thomas Schettgen, Vincent Brandenburg, Danilo Fliser, Cees Vermeer, Jürgen Floege, Georg Schlieper, Thilo Krüger
• Journal: Kidney international (Kidney Int) Vol. 86 Issue 2 Pg. 286-93 (Aug 2014) ISSN: 1523-1755 [Electronic] United States
• PMID: 24429407 (Publication Type: Journal Article)

Chemical References

• Calcium-Binding Proteins
• Extracellular Matrix Proteins
• matrix Gla protein
• Vitamin K 2
• Vitamin K
• Vitamin K 1
• NAD(P)H Dehydrogenase (Quinone)
• Carbon-Carbon Ligases
• glutamyl carboxylase

Topics

• Animals
• Aorta (metabolism)
• Calcinosis (etiology, metabolism, prevention & control)
• Calcium-Binding Proteins (blood)
• Carbon-Carbon Ligases (genetics, metabolism)
• Extracellular Matrix Proteins (blood)
• Kidney (metabolism)
• Liver (metabolism)
• Male
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Rats
• Rats, Wistar
• Uremia (complications, drug therapy, metabolism)
• Vitamin K (administration & dosage, metabolism)
• Vitamin K 1 (metabolism)
• Vitamin K 2 (metabolism)
• Vitamin K Deficiency (blood, metabolism)