Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure

Aegida Neradova, Grzegorz Wasilewski, Selene Prisco, Peter Leenders, Marjolein Caron, Tim Welting, Bert van Rietbergen, Rafael Kramann, J. rgen Floege, Marc G. Vervloet, Leon J. Schurgers

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11 Citations (Scopus)


Background: Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. Methods: We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (μCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. Results: The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by μCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. Conclusion: In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Original languageEnglish
Pages (from-to)652-662
Number of pages11
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Issue number4
Early online date30 Oct 2021
Publication statusPublished - 1 Apr 2022


  • chronic kidney disease
  • matrix Gla protein
  • phosphate binders
  • vascular calcification
  • vitamin K2

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