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.

Conclusion: 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.