Skip to main content

Advertisement

Log in

The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients.

Methods

We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 μgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up.

Results

There were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups.

Conclusions

Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. London G, Guerin A, Marchais S et al (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. NDT 18(9):1731–1740. https://doi.org/10.1093/ndt/gfg414

    Article  PubMed  Google Scholar 

  2. Russo D, Corrao S, Battaglia Y et al (2011) Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis. Kidney Int 80(1):112–118. https://doi.org/10.1038/ki.2011.69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Paloian N, Giachelli C (2014) A current understanding of vascular calcification in CKD. Am J Physiol Renal Physiol 307(8):F891–F900. https://doi.org/10.1152/ajprenal.00163.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Speer M, Giachelli C (2004) Regulation of cardiovascular calcification. Cardiovasc Pathol 13(2):63–70. https://doi.org/10.1016/S1054-8807(03)00130-3

    Article  CAS  PubMed  Google Scholar 

  5. Sage A, Tintut Y, Demer L (2010) Regulatory mechanisms in vascular calcification. Nat Rev Cardiol 7:528–536. https://doi.org/10.1038/nrcardio.2010.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Boström K, Watson K, Horn S et al (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 91(4):1800–1809. https://doi.org/10.1172/JCI116391

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ewence A, Bootman M, Roderick L et al (2008) Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 103(5):28–34. https://doi.org/10.1161/CIRCRESAHA.108.181305

    Article  CAS  Google Scholar 

  8. Shroff R, Shanahan C (2007) The vascular biology of calcification. Semin Dial 20:103–109. https://doi.org/10.1111/j.1515-139X.2007.00255.x

    Article  PubMed  Google Scholar 

  9. Delanaye P, Krzesinski JM, Warling X et al (2014) Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients. BMC Nephrol 15:145. https://doi.org/10.1186/1471-2369-15-145

    Article  PubMed  PubMed Central  Google Scholar 

  10. Schurgers J, Cranenburg C, Vermeer C (2008) Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost 100(4):593–603. https://doi.org/10.1160/TH08-02-0087

    Article  CAS  PubMed  Google Scholar 

  11. Fang-Fei W, Trenson S, Thijs L et al (2018) Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population. Nephrol Dial Transplant 33(7):1122–1128. https://doi.org/10.1093/ndt/gfx258

    Article  CAS  Google Scholar 

  12. Zebboudj F, Imura M, Bostrom K (2002) Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2. J Biol Chem 277(6):4388–4394. https://doi.org/10.1074/jbc.M109683200

    Article  CAS  PubMed  Google Scholar 

  13. Stafford D (2005) The vitamin K cycle. J Thromb Haemost 3(8):1873–1878. https://doi.org/10.1111/j.1538-7836.2005.01419

    Article  CAS  PubMed  Google Scholar 

  14. Cranenburg E, Schurgers J, Uiterwijk H et al (2012) Vitamin K intake and status are low in hemodialysis patients. Kidney Int 82(5):605–610. https://doi.org/10.1038/ki.2012.191

    Article  CAS  PubMed  Google Scholar 

  15. Dalmeijer G, van der Schouw Y, Magdeleyns E et al (2012) The effect of menaquinone-7 supplementation on circulating species. Atherosclerosis 225(2):397–402. https://doi.org/10.1016/j.atherosclerosis.2012.09.019

    Article  CAS  PubMed  Google Scholar 

  16. Berkner K, Runge K (2004) The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost 2(12):2118–2132. https://doi.org/10.1111/j.1538-7836.2004.00968.x

    Article  CAS  PubMed  Google Scholar 

  17. Schurgers J, Teunissen J, Hamulyak K et al (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109(8):3279–3283. https://doi.org/10.1182/blood-2006-08-040709

    Article  CAS  PubMed  Google Scholar 

  18. Westenfeld R, Krueger T, Schlieper G et al (2012) Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis 59(2):186–195. https://doi.org/10.1053/j.ajkd.2011.10.041

    Article  CAS  PubMed  Google Scholar 

  19. Caluwé R, Vandecasteele S, Van Vlem B et al (2014) Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant 29(7):1385–1390. https://doi.org/10.1093/ndt/gft464

    Article  CAS  PubMed  Google Scholar 

  20. Braam A, Hoeks P, Brouns F et al (2004) Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost 91(2):373–380. https://doi.org/10.1160/TH03-07-0423

    Article  CAS  PubMed  Google Scholar 

  21. Agatston A, Janowitz W, Hildner F et al (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15(4):827–832. https://doi.org/10.1016/0735-1097(90)90282-T

    Article  CAS  PubMed  Google Scholar 

  22. Giachelli C (2009) The emerging role of phosphate in vascular calcification. Kidney Int 75:890–897. https://doi.org/10.1038/ki.2008.644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schlieper G, Brandenburg V, Djuric Z et al (2009) Risk factors for cardiovascular calcifications in non diabetic Caucasian hemodialysis patients. Kidney Blood Press Res 32:161–168. https://doi.org/10.1159/000221064

    Article  PubMed  Google Scholar 

  24. Blacher J, Guerin A, Pannier B et al (2001) Arterial calcifications, arterial stoffness and cardiovascular risk in end-stage renal disease. Hypertension 38:938–942. https://doi.org/10.1161/hy1001.096358

    Article  CAS  PubMed  Google Scholar 

  25. Fusaro M, D’Alessandro C, Noale M et al (2017) Low vitamin K1 intake in haemodialysis patients. Clin Nutr 36(2):601–607. https://doi.org/10.1016/j.clnu.2016.04.024

    Article  CAS  PubMed  Google Scholar 

  26. Schurgers L, Teunissen K, Knapen M et al (2005) Novel conformation-specific antibodies against matrix γ-carboxyglutamic acid (Gla) protein. Arterioscler Thromb Vasc Biol 25:1629–1633. https://doi.org/10.1161/01.ATV.0000173313.46222.43

    Article  CAS  PubMed  Google Scholar 

  27. Aoun M, Makki M, Azar H et al (2017) High dephosphorylated-uncarboxylated MGP in hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial. BMC Nephrol 18(1):191. https://doi.org/10.1186/s12882-017-0609-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Puzantian H, Akers S, Oldland S et al (2018) Circulating dephospho-uncarboxylated matrix gla-protein is associated with kidney dysfunction and arterial stiffness. Am J Hypertens 31(9):988–994. https://doi.org/10.1093/ajh/hpy079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Scheiber D, Veulemans V, Horn P et al (2015) High-dose menaquinone-7 supplementation reduces cardiovascular calcification in a murine model of extraosseous calcification. Nutrients. 7(8):6991–7011. https://doi.org/10.3390/nu7085318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mansour A, Hariri E, Daaboul Y et al (2017) Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial. J Am Soc Hypertens 11(9):589–597. https://doi.org/10.1016/j.jash.2017.07.001

    Article  CAS  PubMed  Google Scholar 

  31. Vossen L, Schurgers L, vanVarik B et al (2015) Menaquinone-7 supplementation to reduce vascular calcification in patients with coronary artery disease: rationale and study protocol (VitaK-CAC trial). Nutrients 7(11):8905–8915. https://doi.org/10.3390/nu7115443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Solgar Inc., USA, for kindly providing to all participants in the study, the Solgar Vitamin K2 100 mg preparation, free of charge.

Funding

Authors received no funding for this study. Solgar Inc. USA provided the Vitamin K2 preparation for free.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evangelos Papachristou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oikonomaki, T., Papasotiriou, M., Ntrinias, T. et al. The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial. Int Urol Nephrol 51, 2037–2044 (2019). https://doi.org/10.1007/s11255-019-02275-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-019-02275-2

Keywords

Navigation