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Kidney Int. 2014 Aug;86(2):286-93. doi: 10.1038/ki.2013.530. Epub 2014 Jan 15.

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

Author information

1
Department of Nephrology, RWTH University Hospital Aachen, Aachen, Germany.
2
VitaK BV, University of Maastricht, Maastricht, The Netherlands.
3
Department of Environmental and Social Medicine, University Hospital of the RWTH Aachen, Aachen, Germany.
4
Department of Cardiology, RWTH University Hospital Aachen, Aachen, Germany.
5
Department of Internal Medicine IV, Saarland University Medical Centre, Homburg, Germany.

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.

PMID:
24429407
DOI:
10.1038/ki.2013.530
[Indexed for MEDLINE]
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