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 8.9years 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 1.36ml/min/1.73 m² [95% confidence interval (CI) 0.55–2.17ml/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.