Nigwekar Sagar U, Bloch Donald B, Nazarian Rosalynn M, Vermeer Cees, Booth Sarah L, Xu Dihua, Thadhani Ravi I, Malhotra Rajeev
Divisions of *Nephrology,
Rheumatology, Allergy and Immunology, and.
J Am Soc Nephrol. 2017 Jun;28(6):1717-1722. doi: 10.1681/ASN.2016060651. Epub 2017 Jan 3.
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; =0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (=-8.99; =0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.
基质Gla蛋白（MGP）是一种有效的血管钙化抑制剂。MGP抑制钙化的能力需要一种维生素K依赖酶的活性，该酶介导MGP的羧化作用。我们研究了MGP羧化作用如何影响接受透析的成年患者发生钙化防御的风险，并考察了维生素K缺乏对MGP羧化作用的影响。我们的研究纳入了20例发生钙化防御的接受血液透析的患者（病例组）和20例未发生钙化防御的接受血液透析的患者（对照组），两组在年龄、性别、种族和华法林使用情况方面相匹配。病例组的未羧化MGP（ucMGP）和羧化MGP（cMGP）的血浆水平高于对照组。然而，病例组中羧化的MGP占总MGP的比例（相对cMGP浓度 = cMGP/[cMGP + 未羧化MGP]）低于对照组（分别为0.58±0.02和0.69±0.03；P = 0.003）。在未服用华法林的患者中，病例组的相对cMGP浓度同样较低。相对cMGP浓度每降低0.1个单位，钙化防御风险增加两倍多。在多变量调整分析中，维生素K缺乏与较低的相对cMGP浓度相关（β = -8.99；P = 0.04）。总之，维生素K缺乏介导的相对cMGP浓度降低可能在钙化防御的发病机制中起作用。维生素K补充剂能否预防和/或治疗钙化防御需要进一步研究。
