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

Nadine Kaesler, Elke Magdeleyns, Marjolein Herfs, Thomas Schettgen, Vincent Brandenburg, Danilo Flisers, Cees Vermeer, Juergen Floege, Georg Schlieper, Thilo Krueger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 K-1 or K-2 was administered over 4 and 7 weeks. After 4 weeks of adenine diet, the activity of the vitamin K cycle enzyme gamma-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 gamma-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 gamma-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.
Original languageEnglish
Pages (from-to)286-293
JournalKidney International
Volume86
Issue number2
DOIs
Publication statusPublished - Aug 2014

Keywords

  • gamma-carboxylase
  • nephropathy
  • vascular calcification
  • vitamin K

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