Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.
Nephrol Dial Transplant. 2018 Jul 1;33(7):1122-1128. doi: 10.1093/ndt/gfx258.
Recent studies showing an inverse association between estimated glomerular filtration rate (eGFR), a microvascular trait, and inactive desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) support the hypothesis that after vitamin K-dependent activation, matrix Gla protein (MGP) is renoprotective, but these were limited by their cross-sectional design.
In 1009 randomly recruited Flemish (50.6% women), we assessed the association between eGFR and plasma dp-ucMGP, using multivariable-adjusted analyses.
From baseline to follow-up 8.9 years later (median), dp-ucMGP increased by 23.0% whereas eGFR decreased by 4.05 mL/min/1.73 m2 (P < 0.001). In 938 participants with baseline eGFR ≥60 mL/min/1.73 m2, the incidence of eGFR <60 mL/min/1.73 m2 at follow-up was 8.0% versus 4.1% in the top versus the bottom halve of baseline dp-ucMGP. For a 5-fold higher plasma dp-ucMGP at baseline, eGFR at follow-up decreased by 3.15 mL/min/1.73 m2 [95% confidence interval (CI) 1.26-5.05; P = 0.001]. The hazard ratio expressing the risk of progression to eGFR <60 mL/min/1.73 m2 was 3.49 (95% CI 1.45-8.40; P = 0.005). The hazard ratio relating the presence of microalbuminuria at follow-up to baseline dp-ucMGP was 4.70 (95% CI 1.57-14.1; P = 0.006).
In conclusion, circulating inactive dp-ucMGP, a biomarker of poor vitamin K status, predicts renal dysfunction. Possible underlying mechanisms include protection by activated MGP against calcification and inhibition of the bone morphogenetic protein-signalling pathway.
最近的研究表明，肾小球滤过率（eGFR）与无活性去磷酸化未羧化基质 Gla 蛋白（dp-ucMGP）之间呈负相关，提示维生素 K 依赖性激活后，基质 Gla 蛋白（MGP）具有肾脏保护作用，但这些研究受到其横断面设计的限制。
在 1009 名随机招募的佛兰芒人（50.6%为女性）中，我们使用多变量调整分析评估了 eGFR 与血浆 dp-ucMGP 之间的关系。
从基线到 8.9 年后的随访（中位数），dp-ucMGP 增加了 23.0%，而 eGFR 下降了 4.05 mL/min/1.73 m2（P < 0.001）。在基线 eGFR≥60 mL/min/1.73 m2 的 938 名参与者中，与基线 dp-ucMGP 上半部分相比，随访时 eGFR <60 mL/min/1.73 m2 的发生率分别为 8.0%和 4.1%。基线时 dp-ucMGP 升高 5 倍，随访时 eGFR 下降 3.15 mL/min/1.73 m2[95%置信区间（CI）1.26-5.05；P = 0.001]。表达进展为 eGFR <60 mL/min/1.73 m2 的风险比为 3.49（95%CI 1.45-8.40；P = 0.005）。与基线 dp-ucMGP 相关的随访时微量白蛋白尿的风险比为 4.70（95%CI 1.57-14.1；P = 0.006）。
总之，循环无活性 dp-ucMGP，一种维生素 K 状态不良的生物标志物，可预测肾功能障碍。潜在的机制可能包括激活 MGP 对钙化的保护作用和抑制骨形态发生蛋白信号通路。
