Vitamin K and cardiovascular complications in chronic kidney disease patients.

Abstract Vitamin K, well known for its role in coagulation, encompasses two 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 γ-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 CKD patients, in particular the prevention of osteoporosis is still not firmly established. Here we focus on another prominent action of vitamin K, in particular vitamin K2, namely the activation of matrix Gla protein (MGP), 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 (CKD) 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 (MK7), can potently reduce circulating levels of dephosphorylated uncarboxylated, i.e. inactive MGP in patients with end stage kidney disease. However, despite this compelling data basis, several randomized controlled trials with high dose MK7 supplements in patients with advanced CKD have failed to confirm cardiovascular benefits. Here we discuss potential reasons and solutions for this.