Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial

T. Saritas, S. Reinartz, T. Kruger, M. Ketteler, O. Liangos, L. Labriola, P. Stenvinkel, C. Kopp, R. Westenfeld, P. Evenepoel, R. Siepmann, S. Wied, R.D. Hilgers, L. Schurgers, J. Floege*, VitaVasK Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Lay Summary Patients on chronic dialysis exhibit extensive cardiovascular calcifications and vitamin K deficiency. The vitamin K-dependent matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The multicentre, randomized, open-label, controlled VitaVasK trial showed marked attenuation of cardiovascular calcification progression in chronic haemodialysis patients treated with vitamin K1. Vitamin K1 supplementation greatly increased the serum vitamin K concentration and reduced inactive MGP levels. The treatment was safe, as no adverse advents were noted. Larger randomized controlled trials are needed to confirm vitamin K1 therapy as a safe, potent and cost-effective treatment option to reduce the progression of vascular calcification in haemodialysis patients.Background Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Haemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicentre VitaVasK trial analysed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CACs) and thoracic aortic calcifications (TACs). Methods Patients with pre-existing CACs were randomized to continue on standard care or to additionally receive 5 mg of vitamin K1 orally thrice weekly. Hierarchically ordered primary endpoints were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline and 12 and 18 months assessed treatment effects after adjusting for study site. Results Of 60 randomized patients, 20 dropped out for reasons unrelated to vitamin K1, resulting in 23 control and 17 vitamin K1 patients. The trial was stopped early due to slow recruitment. At 18 months, the average TAC progression was 56% lower in the vitamin K1 compared with the control group (p = .039). CAC significantly progressed within the control group, but not within the vitamin K1 group. Average progression at 18 months was 68% lower in the vitamin K1 compared to the control group (P = .072). Vitamin K1 reduced plasma levels of pro-calcific uncarboxylated MGP by 69% at 18 months. No treatment-related adverse events were noted. Conclusion Vitamin K1 intervention is a potent, safe and cost-effective approach to correct vitamin K deficiency and to potentially reduce cardiovascular calcification in this high-risk population.
Original languageEnglish
Pages (from-to)2300-2311
Number of pages12
JournalClinical Kidney Journal
Volume15
Issue number12
Early online date24 Aug 2022
DOIs
Publication statusPublished - 27 Nov 2022

Keywords

  • matrix Gla protein
  • valvular calcification
  • vascular calcification
  • vitamin K
  • CHRONIC KIDNEY-DISEASE
  • CORONARY-ARTERY CALCIUM
  • MATRIX GLA PROTEIN
  • K SUPPLEMENTATION
  • VASCULAR CALCIFICATION
  • PEOPLE
  • RISK

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