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Abstract: TH-PO553

Combining Phosphate Binder Therapy with High Vitamin K2 Diet Inhibits Vascular Calcification in an Experimental CKD Animal Model

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Neradova, Aegida, Amsterdam University Medical Center, Overveen, Netherlands
  • Wasilewski, Grzegorz Boguslaw, Maastricht University, Maastricht, Netherlands
  • Prisco, Selene, Maastricht University, Maastricht, Netherlands
  • Caron, Marjolein M.j., Maastricht University Medical Center, Maastricht, Netherlands
  • Welting, Tim Jm, Maastricht University Medical Center, Maastricht, Netherlands
  • Rietbergen, Bert Van, University of Technology, Eindhoven, Netherlands
  • Kramann, Rafael, RWTH Aachen University, Lemiers, Netherlands
  • Floege, Jürgen, RWTH University of Aachen, Aachen, Germany
  • Vervloet, Marc G., Amsterdam University Medical Center, Overveen, Netherlands
  • Schurgers, Leon J., Maastricht University, Maastricht, Netherlands
Background

Hyperphosphatemia may contribute to cardiovascular disease and mortality. Therefore, phosphate binders (PB) are widely used, but a proof of risk reduction is lacking. By binding vitamin K PB may offset beneficial effects of phosphate reduction on vascular calcification (VC). Here we tested whether high vitamin K2 supplementation in combination with PB can inhibit VC in an experimental animal model for CKD.

Methods

Description of the model (Figure 1). Blood chemistry was analyzed to verify the CKD model. Aortic arch, abdominal aorta and cartilage was analyzed for calcification using high resolution micro CT scan (in parafin embeded aortas and formalin fixed tibia's) and by inactive ucMGP using conformation specific antibodies.

Results


3/4Nx resulted in increased circulating creatinine (mmol/L) and urea (mmol/L) (p < 0.01 for both). PB combined with low vitamin K2 diet resulted in significant vascular and cartilage calcification. On the contrary, PB combined with high vitamin K2 revealed significantly less ectopic calcification. Immunohistochemical staining of tissues for ucMGP revealed that ucMGP was present at sites of vascular calcification, mainly in the low vitamin K2 treated groups, indicating severe vascular vitamin K deficiency (Figure 2).

Conclusion

These experiments demonstrate that PB therapy in CKD cannot prevent VC, but that the combination with high vitamin K2 did. The inhibitory effect on vascular and cartilage calcification of combined phosphate binder with vitamin K2 therapy lies in the synergy of phosphate control and correction of vitamin K deficiency.

Figure 1

Figure 2

Funding

  • Private Foundation Support