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Zaragatski, Emma; Grommes, Jochen; Schurgers, Leon J.; Langer, Stephan; Kennes, Lieven; Tamm, Miriam; Koeppel, Thomas A.; Kranz, Jennifer; Hackhofer, Tina; Arakelyan, Karen; Jacobs, Michael J.; Kokozidou, Maria (2016): Vitamin K antagonism aggravates chronic kidney disease-induced neointimal hyperplasia and calcification in arterialized veins: role of vitamin K treatment? In: Kidney international, Vol. 89, No. 3: pp. 601-611
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Arteriovenous fistula (AVF) is the common vascular access type for a hemodialysis patient. Its failure is due to neointimal hyperplasia. Vitamin K antagonists are given to lower thrombosis tendency, but have side effects that enhance arterial calcifications. Here, we investigated the effects of vitamin K antagonists and vitamin K2 (K2) treatment on neointimal hyperplasia development and calcification in rats and in arterialized human veins. AVF was generated in female rats while chronic kidney disease (CKD) was induced using an adenine-enriched diet. Arterialization, CKD, and vitamin K antagonists all significantly enhanced venous neointimal hyperplasia. K2 treatment, additional to vitamin K antagonists, significantly reduced neointimal hyperplasia in arterialized veins in healthy rats but not in rats with CKD. Arterialization, CKD, and vitamin K antagonism all significantly increased, whereas K2 supplementation attenuated calcification in healthy rats and rats with CKD. K2 significantly enhanced matrix Gla protein carboxylation in control rats and rats with CKD. Arterialized human vein samples contained inactive matrix Gla protein at calcification and neointimal hyperplasia sites, indicating local vitamin K deficiency. Thus, vitamin K antagonists have detrimental effects on AVF remodeling, whereas K2 reduced neointimal hyperplasia and calcification indicating vasoprotective effects. Hence, K2 administration may be useful to prevent neointimal hyperplasia and calcification in arterialized veins. (C) 2015 International Society of Nephrology