维生素K对CKD-MBD骨代谢异常以及血管钙化的治疗及作用机制

Therapeutical action and mechanism of vitamin K in chronic kidney disease-mineral and bone disorder and vascular calcification

慢性肾脏疾病矿物质和骨异常(chronic kidney disease mineral and bone disorder,CKD-MBD)是慢性肾脏病(chronic kidney disease,CKD)的主要并发症之一,是一种全身性的矿物质和骨代谢障碍,包括钙、磷、甲状旁腺素(PTH)或维生素D代谢异常,骨转换、矿化、骨量、骨的线性生长或强度异常以及血管或其他软组织钙化,增加了CKD患者的心血管风险、骨折风险以及死亡率[1]。临床治疗上以控制钙磷平衡、降低甲状旁腺素、抑制血管钙化为主,包括使用含钙/非含钙磷结合剂、活性维生素D及其类似物、西那卡塞等。维生素K是一组脂溶性维生素,可作为γ-谷氨酰羧化酶(γ-glutamyl carboxylase,GGCX)的辅助因子,该酶通过激活维生素K依赖蛋白(vitamin K-dependent proteins,VKDP)参与凝血因子的活化、凋亡,以及抑制血管钙化、调节骨矿化[2]。越来越多的证据表明,CKD患者患有亚临床维生素K缺乏症,补充维生素K尤其是维生素K2,可增加CKD患者骨强度、抑制血管钙化。本文将从维生素K的缺乏和补充对CKD相关矿物质和骨疾病(CKD-MBD)的影响及其作用机制、临床应用等方面进行阐述。

Chronic kidney disease mineral and bone disorder(CKD-MBD)is a systemic syndrome of mineral and bone metabolism disorders.CKD-MBD is caused by chronic kidney disease(CKD),including abnormalities in the metabolism of calcium,phosphorus,parathyroid hormone(PTH)or vitamin D,abnormal bone turnover,mineralization,bone mass,linear bone growth or strength,and calcification of blood vessels or other soft tissues,which severely increases the risk of cardiovascular disease and fracture,and the mortality of patients with CKD[1].Clinically,calcium-/non-calcium-phosphorus-containing conjugates,active vitamin D and its analogs,and cinacalcet are used to control the calcium-phosphorus imbalance,high parathyroid hormone production,and vascular calcification associated with CKD-MBD.Vitamin K is a liposoluble vitamin that acts as a cofactor forγ-glutamyl carboxylase(GGCX),an enzyme involved in coagulation factor activation,apoptosis,and inhibition of vascular calcification and regulation of bone mineralization through activation of vitamin K-dependent proteins(VKDP)[2].There is increasing evidence that patients with CKD suffer from subclinical vitamin K deficiency.Vitamin K supplementation,especially vitamin K2,increases bone strength and inhibits vascular calcification in CKD patients.Herein,we will discuss the effects and mechanisms of vitamin K deficiency and supplementation on CKD-MBD,and its clinical applications.