P4.4 INHIBITION OF ARTERIAL CALCIFICATION BY MATRIX GLA PROTEIN AS DETERMINANT OF RENAL FUNCTION IN THE GENERAL POPULATION

Abstract

Background: Carboxylation of matrix Gla protein (MGP), a vitamin K dependent process, activates the protein to a powerful inhibitor of arterial calcification. Circulating dephosphorylated and uncarboxylated MGP (dp-ucMGP) and total uncarboxylated MGP (t-ucMGP) are associated with macrovascular disease. The association with microcirculatory disease remains unknown. Methods: In 1174 randomly recruited Flemish (51.4% women; mean age, 38.2 years), we studied the estimated glomerular filtration rate (eGFR) and microalbuminuria, as prototypes of microcirculatory traits, in relation to dp-ucMGP and t-ucMGP. In multivariable linear and logistic regressions, we expressed effect sizes for a doubling of the biomarkers, while accounted for anthropometric characteristics, lifestyle, risk factors and use of medications. Results: Among all participants, geometric means of dp-ucMGP and t-ucMGP were 3.68 mg/L and 45.2 mg/L, respectively. In relation to dp-ucMGP (figure), eGFR decreased by 1.57 mL/min/1.73 m2 (p=0.015), while the risk of renal dysfunction (eGFR <60 mL/min/1.73 m2) increased by 19% (p=0.022) with a 43% trend in the same direction (p=0.069) for microalbuminuria (albumin-to-creatinine ratio ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men). In relation to t-ucMGP (figure), eGFR increased by 1.89 mL/min/1.73 m2 (p=0.041) with no changes in the risks of renal dysfunction or microalbuminuria (p≥0.12). Conclusion: In the general population, eGFR is inversely correlated with dp-ucMGP, a marker of vitamin K deficiency, whereas the opposite is the case for t-ucMGP, a marker of prevalent arterial calcification.