Undercarboxylated Matrix GLA Protein Levels Are Decreased in Dialysis Patients and Related to Parameters of Calcium-Phosphate Metabolism and Aortic Augmentation IndexHermans M.M.H. · Vermeer C. · Kooman J.P. · Brandenburg V. · Ketteler M. · Gladziwa U. · Rensma P.L. · Leunissen K.M.L. · Schurgers L.J.
aDepartment of Internal Medicine and Nephrology, Academic Hospital Maastricht, bCardiovascular Research Institute CARIM, cVitak BV, University of Maastricht, Maastricht, and dDepartment of Internal Medicine and Nephrology, Elisabeth Hospital, Tilburg, The Netherlands; eUniversity of Witten-Herdecke, Witten, and fDepartment of Nephrology and Clinical Immunology, University Hospital RWTH, Aachen, Germany
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 β 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.