Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population

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, matrix Gla protein (MGP) is renoprotective, but these 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 23.0% whereas eGFR decreased by 4.05 mL/min/1.73 m(2) (P < 0.001). In 938 participants with baseline eGFR ≥60 mL/min/1.73 m(2), the incidence of eGFR <60 mL/min/1.73 m(2) at follow-up was 8.0% versus 4.1% in the top versus the bottom halve of baseline dp-ucMGP. For a 5-fold higher plasma dp-ucMGP at baseline, eGFR at follow-up decreased by 3.15 mL/min/1.73 m(2) [95% confidence interval (CI) 1.26–5.05; P = 0.001]. The hazard ratio expressing the risk of progression to eGFR <60 mL/min/1.73 m(2) was 3.49 (95% CI 1.45–8.40; P = 0.005). The hazard ratio relating the presence of microalbuminuria at follow-up to baseline dp-ucMGP was 4.70 (95% CI 1.57–14.1; P = 0.006). 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 the bone morphogenetic protein-signalling pathway.