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循环无活性基质 Gla 蛋白形式是慢性肾脏病血管钙化的替代标志物:初步报告。

The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report.

机构信息

INSERM ERI-12, Divisions of Clinical Pharmacology and Nephrology, Amiens University Hospital, Avenue René Laennec, F-80054 Amiens, France.

出版信息

Clin J Am Soc Nephrol. 2010 Apr;5(4):568-75. doi: 10.2215/CJN.07081009. Epub 2010 Feb 4.

Abstract

BACKGROUND AND OBJECTIVES

Vitamin K-dependent matrix Gla protein (MGP) acts as a calcification inhibitor in vitro and in vivo. The present study was performed to (1) determine plasma levels of the inactive, dephosphorylated, uncarboxylated MGP (dp-ucMGP) in a cohort of patients at different stages of chronic kidney disease (CKD) and (2) evaluate the association between dp-ucMGP levels on one hand and aortic calcification and mortality on the other.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 107 patients (67 +/- 13 years; 60% male; 32% at CKD stages 2 to 3, 31% at stages 4 to 5, 37% at stage 5D) were assayed for dp-ucMGP and underwent multislice spiral computed tomography scans to quantify aortic calcification at baseline. They were prospectively monitored for mortality.

RESULTS

Plasma dp-ucMGP levels augmented progressively with CKD stage, with a significant difference from CKD stage 4. CKD stage, hemoglobin, age, and coumarin use were independently associated with plasma dp-ucMGP levels. Furthermore, plasma dp-ucMGP and age were positively and independently associated with the aortic calcification score. During follow-up (802 +/- 311 days), 34 patients died (20 from cardiovascular events). In a crude analysis, [plasma dp-ucMGP] > 921 pM was associated with overall mortality; this association was lost after adjusting for both age and the calculated propensity score.

CONCLUSIONS

Plasma dp-ucMGP increased progressively in a CKD setting and was associated with the severity of aortic calcification. Plasma dp-ucMGP could thus be a surrogate marker for vascular calcification in CKD.

摘要

背景与目的

维生素 K 依赖的基质 Gla 蛋白(MGP)在体外和体内均具有抗钙化作用。本研究旨在:(1)确定不同慢性肾脏病(CKD)分期患者群体中无活性、去磷酸化、未羧化的 MGP(dp-ucMGP)的血浆水平;(2)评估 dp-ucMGP 水平与主动脉钙化和死亡率之间的关系。

设计、地点、参与者和测量:107 名患者(67 ± 13 岁;60%为男性;32%为 CKD 2 至 3 期,31%为 4 至 5 期,37%为 5D 期)接受 dp-ucMGP 检测,并在基线时接受多层螺旋 CT 扫描以定量主动脉钙化。对他们进行前瞻性监测以评估死亡率。

结果

随着 CKD 分期的进展,血浆 dp-ucMGP 水平逐渐升高,与 CKD 4 期相比差异有统计学意义。CKD 分期、血红蛋白、年龄和香豆素使用与血浆 dp-ucMGP 水平独立相关。此外,血浆 dp-ucMGP 和年龄与主动脉钙化评分呈正相关且独立相关。在随访期间(802 ± 311 天),34 名患者死亡(20 例死于心血管事件)。在未校正分析中,[血浆 dp-ucMGP]>921 pM 与全因死亡率相关;在调整年龄和计算倾向评分后,这种相关性消失。

结论

在 CKD 环境中,血浆 dp-ucMGP 逐渐升高,并与主动脉钙化的严重程度相关。因此,血浆 dp-ucMGP 可能是 CKD 患者血管钙化的替代标志物。

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本文引用的文献

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