Vitamin K and cardiovascular complications in chronic kidney disease patients

N. Kaesler, L.J. Schurgers, J. Floege*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

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Abstract

Vitamin K, well known for its role in coagulation, encompasses 2 major subgroups: vitamin K1 is exclusively synthesized by plants, whereas vitamin K2 mostly originates from bacterial synthesis. Vitamin K serves as a cofactor for the enzyme gamma-glutamyl carboxylase, which carboxylates and thereby activates various vitamin K-dependent proteins. Several vitamin K-dependent proteins are synthesized in bone, but the role of vitamin K for bone health in chronic kidney disease patients, in particular the prevention of osteoporosis, is still not firmly established. Herein, we focus on another prominent action of vitamin K, in particular vitamin K2 (namely, the activation of matrix gamma-carboxyglutamic acid protein, the most potent inhibitor of cardiovascular calcifications). Multiple observational studies link relative vitamin K deficiency or low intake to cardiovascular calcification progress, morbidity, and mortality. Patients with advanced chronic kidney disease are particularly vitamin K deficient, in part because of dietary restrictions but possibly also due to impaired endogenous recycling of vitamin K. At the same time, this population is characterized by markedly accelerated cardiovascular calcifications and mortality. High-dose dietary supplementation with vitamin K2, in particular the most potent form, menaquinone 7, can potently reduce circulating levels of dephosphorylated uncarboxylated (i.e., inactive matrix gamma-carboxyglutamic acid protein) in patients with end-stage kidney disease. However, despite this compelling data basis, several randomized controlled trials with high-dose menaquinone 7 supplements in patients with advanced chronic kidney disease have failed to confirm cardiovascular benefits. Herein, we discuss potential reasons and solutions for this.
Original languageEnglish
Pages (from-to)1023-1036
Number of pages14
JournalKidney International
Volume100
Issue number5
DOIs
Publication statusPublished - 1 Nov 2021

Keywords

  • calcification
  • cardiovascular disease
  • lipoproteins
  • matrix Gla protein
  • vitamin K
  • MATRIX GLA-PROTEIN
  • ORAL ANTICOAGULANT TREATMENT
  • GAMMA-CARBOXYGLUTAMIC ACID
  • CORONARY-HEART-DISEASE
  • VASCULAR CALCIFICATION
  • HEMODIALYSIS-PATIENTS
  • DIETARY-INTAKE
  • MENAQUINONE-7 SUPPLEMENTATION
  • DEPENDENT CARBOXYLATION
  • PLASMA PHYLLOQUINONE

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