The Circulating Inactive Form of Matrix Gla Protein Is a... : Clinical Journal of the American Society of Nephrology (original) (raw)

Original Articles: Original Articles

The Circulating Inactive Form of Matrix Gla Protein Is a Surrogate Marker for Vascular Calcification in Chronic Kidney Disease

A Preliminary Report

Schurgers, Leon J.*; Barreto, Daniela V.†,‡; Barreto, Fellype C.†,‡; Liabeuf, Sophie†,‡; Renard, Cédric§; Magdeleyns, Elke J.*; Vermeer, Cees*; Choukroun, Gabriel†,‖; Massy, Ziad A.†,‡,‖

*Cardiovascular Research Institute Maastricht and VitaK, University of Maastricht, Maastricht, the Netherlands;

†Institut National de la Santé et de la Recherche Médicale ERI-12 (EA 4292), Amiens, France;

‡Division of Clinical Pharmacology, Clinical Research Centre, Amiens University Hospital and the Jules Verne University of Picardie, Amiens, France; and

Divisions of §Radiology and

‖Nephrology, Amiens University Hospital, Amiens, France

Correspondence: Dr. Ziad A. Massy, INSERM ERI-12, Divisions of Clinical Pharmacology and Nephrology, Amiens University Hospital, Avenue René Laennec, F-80054 Amiens, France. Phone: +33-322-455788; Fax: +33-322-455660; E-mail: [email protected]

L.J.S. and D.V.B. contributed equally to this work.

F.C.B. and S.L. contributed equally to this work.

Received October 6, 2009

Accepted December 30, 2009

Clinical Journal of the American Society of Nephrology 5(4):p 568-575, April 2010. | DOI: 10.2215/CJN.07081009

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.