Kidney International study highlights Vitamin K2 more effective reducing AVF failure.
Kidney International, a journal of the Nature group and the International Society of Nephrology, has approved for publication in October 2015 a new paper showing the protective effect vitamin K2 on arteriovenous fistula failure, a common complication suffered by chronic kidney disease (CKD) patients requiring hemodialysis.
Insights on the study
The study, “Vitamin K- antagonist aggravate CKD induced neointimal hyperplasia and calcification in arterialized veins: potential role for vitamin K2 to prevent AVF failure”, is significant because it adds to the growing body of evidence demonstrating the dangers of vitamin K antagonists (i.e., oral anticoagulants), a common traditional cardiovascular therapy inducing severe vitamin K deficiency, and how vitamin K2 provides an alternative impactful therapy to combat vascular damage.
“Arteriovenous fistula (AVFs) is a frequently used vascular access type for chronic kidney disease patients requiring hemodialysis. AVF failure is a complication leading to high hospitalization rates and morbidity. Whereas early AVF failure is caused by thrombosis or the veins’ inability to dilate, later-course AVF failure is induced by stenosis and thrombosis resulting from neointimal hyperplasia (NIH) and calcification,” says Dr. Leon Schurgers, associate professor and senior scientist at the department of biochemistry, the Cardiovascular Research Institute CARIM of University of Maastricht (The Netherlands), and researcher on the study. “Vascular calcification is a frequent complication in CKD patients; diagnosed as arterial calcification and calcification of arterialized veins. Recent work indicates that AVF calcification contributes to AVF failure.”
Dr. Schurgers notes that CKD patients have significantly lower circulating vitamin K concentrations compared to the general population and hemodialysis patients have a poor overall vitamin K status due to low vitamin K intake. In addition, a high number of CKD patients at risk of arterial and venous thrombosis receive oral anticoagulants (vitamin K-antagonists; VKA). VKAs interfere with carboxylation of coagulation factors, but also impair the activation of Matrix Gla Protein (MGP), a vitamin K-dependent protein produced by vascular smooth muscle cells that is a powerful vascular calcification inhibitor.
“These constellations make CKD patients and patients undergoing VKA therapy, such as warfarin, prone to vascular calcification,” he explains. “Treatment of CKD patients with vitamin K2 has been a suggested option to inhibit vascular calcification by counteracting the vitamin K deficiency.”
To that end, AVF was generated in 190 rats. CKD was induced using adenine-enriched diet. Effects of CKD, VKA and K2 on AVF remodeling were evaluated using histology, morphometric analysis and immunohistochemistry. Examination of native and arterialized human veins was performed.
Results showed that arterialization, CKD and VKA significantly enhanced AVF failure. K2 supplementation reduced AVF failure in healthy and CKD animals.
Vitamin K2 – a way to prevent AVF failure
The data showed that K2 enhanced matrix Gla protein (MGP) carboxylation in control and CKD animals. Human vein samples showed inactive MGP at calcification and NIH sites, indicating local vitamin K-deficiency. “We show that VKA treatment has detrimental effects on AVF remodeling,” says Dr. Schurgers. “K2 supplementation reduced NIH and calcification – and thus AVF failure – indicating vasoprotective effects. In arterialized veins, K2 should be considered as therapeutic approach to prevent AVF failure.”
“Clearly oral anticoagulant vitamin K antagonists thin blood at the expense of other essential metabolic functions, such as proper calcium utilization for bone support and cardiovascular protection,” says Hogne Vik, CEO of ex-NattoPharma, makers of MenaQ7® Vitamin K2 as MK-7. “It is time the medical community change the standard of care away from ‘rat poison.’”
Zaragatski E, Grommes J, Schurgers LJ, Langer S, Kees L, Tamm M, Koeppel TA, Kranz J, Hackhofer T, Arakelyan K, Jacobs MJ, Kokozidou M. Vitamin K- antagonist aggravate CKD induced neointimal hyperplasia and calcification in arterialized veins: potential role for vitamin K2 to prevent AVF failure. Kidney Int. 2016 Mar;89(3):601-11.