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

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.

Figures

Figure 1.

Plasma dp-ucMGP levels by CKD stage. *P < 0.001 versus CKD stages 2 and 3. The dotted lines indicate the upper and lower boundaries of the plasma dp-ucMGP range in age-matched controls.

Figure 2.

Exponential relationship between plasma dp-ucMGP levels and the estimated GFR, for patients at CKD stages 2 to 5 (n = 67), r2 = 0.268, P < 0.0001.

Figure 3.

Linear relationship between aortic calcification score and plasma dp-ucMGP levels (n = 101), r2 = 0.143, P < 0.0001.

Figure 4.

Kaplan-Meier estimates of overall mortality as a function of the median plasma dp-ucMGP level.