Undercarboxylated matrix GLA protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index.
BACKGROUND
Vascular calcifications are related to cardiovascular mortality and morbidity in dialysis patients. Limited data exist on the role of calcification inhibitors, such as matrix-carboxyglutamic acid protein (MGP) in dialysis patients.


METHODS
In 120 dialysis patients and 41 age-matched healthy controls, circulating undercarboxylated (uc) MGP levels were measured with a novel ELISA-based competitive assay. The association between ucMGP levels and determinants of bone mineral metabolism, including the calcification inhibitor fetuin-A, was studied. Moreover, the relation between ucMGP levels and arterial stiffness was investigated.


RESULTS
The ucMGP level was significantly lower in dialysis patients compared to controls (173 +/- 70 vs. 424 +/- 126 nmol/l; p < 0.0001). After adjustment for age, sex and duration of dialysis an independent negative association between time-averaged phosphate levels [regression coefficient beta with 95% confidence interval = -64 (-107 to -21)] and a positive association between serum ucMGP and fetuin-A [131 (55-208)] was observed. Duration of dialysis was inversely correlated with ucMGP (r = -0.24, p = 0.007). ucMGP levels were not related to high-sensitivity C-reactive protein or time-averaged calcium levels. After adjustment for age, sex, cardiovascular disease, diabetes, height and mean arterial pressure, ucMGP level was negatively associated with the aortic augmentation index [-0.036 (-0.061 to -0.010)] but not with pulse wave velocity or pulse pressure.


CONCLUSIONS
Significantly lower serum ucMGP levels were observed in dialysis patients compared to healthy controls. ucMGP levels were inversely associated with phosphate and positively associated with serum fetuin-A levels. Furthermore, ucMGP levels were inversely associated with the aortic augmentation index. These data suggest that low ucMGP levels may be a marker of active calcification.
Hermans
Marc M H
MM
Department of Internal Medicine and Nephrology, Academic Hospital Maastricht, Maastricht, The Netherlands. mherm@sint.azm.nl
Vermeer
Cees
C
Kooman
Jeroen P
JP
Brandenburg
Vincent
V
Ketteler
Markus
M
Gladziwa
Ulrich
U
Rensma
Pieter L
PL
Leunissen
Karel M L
KM
Schurgers
Leon J
LJ
D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure; D002113:Calcification, Physiologic; D002130:Calcium Phosphates / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000737:chemistry; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000737:chemistry; D006801:Humans; D006435:Renal Dialysis; D000509:alpha-Fetoproteins / Q000032:analysis; D000097568:Matrix Gla Protein
D002130:Calcium Phosphates; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000509:alpha-Fetoproteins; D000097568:Matrix Gla Protein; C020243:calcium phosphate