1.5 DESPHOSPHO-UNCARBOXYLATED MATRIX GLA PROTEIN IS A NOVEL CIRCULATING BIOMARKER PREDICTING DETERIORATION OF RENAL FUNCTION IN THE GENERAL POPULATION

Abstract

Background: Recent studies showing an inverse association between estimated glomerular filtration rate (eGFR), a microvascular trait, and inactive desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) support the hypothesis that after vitamin K dependent activation MGP is renoprotective, but were limited by their cross-sectional design. Methods: In 1009 randomly recruited Flemish (50.6% women), we assessed the association between eGFR and plasma dp-ucMGP, using multivariable-adjusted analyses. Results: From baseline to follow-up 8.9 years later (median), dp-ucMGP increased by 3.7%, whereas eGFR decreased by 4.05 ml/min/1.73 m2 (P < 0.001). In 938 participants with baseline eGFR ≥ 60 ml/min/1.73 m2, incidence of eGFR < 60 ml/min/1.73 m2 at follow-up was 8.0% vs. 4.1% in the top vs. the bottom halve of baseline dp-ucMGP. For each doubling of baseline dp-ucMGP, eGFR at follow-up decreased by 1.36 ml/min/1.73 m2 [95% confidence interval (CI) 0.55–2.17 ml/min/1.73 m2; P = 0.001]. The hazard ratio expressing the risk of progression to eGFR < 60 ml/min/1.73 m2 was 1.67 (95% CI 1.16–2.41; P = 0.006). The hazard ratio relating the presence of microalbuminuria at follow-up to baseline dp-ucMGP was 1.96 (95% CI 1.22–3.12; P = 0.005). Conclusions: In conclusion, circulating inactive dp-ucMGP, a biomarker of poor vitamin K status, predicts renal dysfunction. Possible underlying mechanisms include protection by activated MGP against calcification and inhibition of bone morphogenetic protein signaling pathway.