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


METHODS
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.
INSERM ERI-12, Divisions of Clinical Pharmacology and Nephrology, Amiens University Hospital, Avenue René Laennec, F-80054 Amiens, France.
Leon J
LJ
Schurgers
Daniela V
DV
Barreto
Fellype C
FC
Barreto
Sophie
S
Liabeuf
Cédric
C
Renard
Elke J
EJ
Magdeleyns
Cees
C
Vermeer
Gabriel
G
Choukroun
Ziad A
ZA
Massy
D000368:Aged; D000369:Aged, 80 and over; D001018:Aortic Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality; D001027:Aortography / Q000379:methods; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality; D002135:Calcium-Binding Proteins / Q000097:blood*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D036542:Tomography, Spiral Computed; D015854:Up-Regulation; D000097568:Matrix Gla Protein
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein