Division of Nephrology, Department of Internal Medicine, OLVZ Aalst, Belgium.
Division of Nephrology, Department of Internal Medicine, University Hospital, Ghent, Belgium.
Nephrol Dial Transplant. 2020 Jan 1;35(1):23-33. doi: 10.1093/ndt/gfy373.
The cardinal biological role of vitamin K is to act as cofactor for the carboxylation of a number of vitamin K-dependent proteins, some of which are essential for coagulation, bone formation and prevention of vascular calcification. Functional vitamin K deficiency is common and severe among dialysis patients and has garnered attention as a modifiable risk factor in this population. However, no single biochemical parameter can adequately assess vitamin K status. For each biological function of vitamin K, the degree of carboxylation of the relevant vitamin K-dependent protein most accurately reflects vitamin K status. Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) is the best biomarker for vascular vitamin K status when cardiovascular endpoints are studied. Dp-ucMGP levels are severely elevated in haemodialysis patients and correlate with markers of vascular calcification and mortality in some but not all studies. The aetiology of vitamin K deficiency in haemodialysis is multifactorial, including deficient intake, uraemic inhibition of the vitamin K cycle and possibly interference of vitamin K absorption by phosphate binders. The optimal vitamin K species, dose and duration of supplementation to correct vitamin K status in dialysis patients are unknown. Dp-ucMGP levels dose-proportionally decrease with supraphysiological vitamin K2 supplementation, but do not normalize even with the highest doses. In the general population, long-term vitamin K1 or K2 supplementation has beneficial effects on cardiovascular disease, bone density and fracture risk, and insulin resistance, although some studies reported negative results. In haemodialysis patients, several trials on the effects of vitamin K on surrogate markers of vascular calcification are currently ongoing.
维生素 K 的主要生物学作用是作为一些维生素 K 依赖蛋白羧化作用的辅助因子，其中一些蛋白对凝血、骨形成和防止血管钙化至关重要。透析患者中功能性维生素 K 缺乏很常见且严重，已引起关注，认为这是该人群中可改变的危险因素。然而，没有单一的生化参数可以充分评估维生素 K 状态。对于维生素 K 的每一种生物学功能，相关维生素 K 依赖蛋白的羧化程度最能反映维生素 K 状态。去磷酸化未羧化基质 Gla 蛋白（dp-ucMGP）是研究心血管终点时血管维生素 K 状态的最佳生物标志物。在血液透析患者中，dp-ucMGP 水平显著升高，并且与一些但不是所有研究中的血管钙化和死亡率标志物相关。血液透析患者维生素 K 缺乏的病因是多因素的，包括摄入不足、尿毒症抑制维生素 K 循环以及可能的磷酸盐结合剂干扰维生素 K 吸收。纠正透析患者维生素 K 状态的最佳维生素 K 种类、剂量和补充持续时间尚不清楚。超生理剂量的维生素 K2 补充可使 dp-ucMGP 水平按比例降低，但即使使用最高剂量也无法使其正常化。在普通人群中，长期补充维生素 K1 或 K2 对心血管疾病、骨密度和骨折风险以及胰岛素抵抗有益，尽管一些研究报告了负面结果。在血液透析患者中，目前正在进行几项关于维生素 K 对血管钙化替代标志物影响的试验。
