TY - JOUR
T1 - Vitamin K and cardiovascular complications in chronic kidney disease patients
AU - Kaesler, N.
AU - Schurgers, L.J.
AU - Floege, J.
N1 - Funding Information:
LJS received institutional grants from Bayer, Boehringer Ingelheim, NattoPharma, and IDS. All the other authors declared no competing interests.
Funding Information:
We apologize to all authors whose important work we could not cite because of space restrictions. This work was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation), TRR 219, C1–Project-ID 322900939.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - calcification
KW - cardiovascular disease
KW - lipoproteins
KW - matrix Gla protein
KW - vitamin K
KW - MATRIX GLA-PROTEIN
KW - ORAL ANTICOAGULANT TREATMENT
KW - GAMMA-CARBOXYGLUTAMIC ACID
KW - CORONARY-HEART-DISEASE
KW - VASCULAR CALCIFICATION
KW - HEMODIALYSIS-PATIENTS
KW - DIETARY-INTAKE
KW - MENAQUINONE-7 SUPPLEMENTATION
KW - DEPENDENT CARBOXYLATION
KW - PLASMA PHYLLOQUINONE
U2 - 10.1016/j.kint.2021.06.037
DO - 10.1016/j.kint.2021.06.037
M3 - (Systematic) Review article
C2 - 34310988
SN - 0085-2538
VL - 100
SP - 1023
EP - 1036
JO - Kidney International
JF - Kidney International
IS - 5
ER -