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Nephrol Dial Transplant. 2018 Jul 1;33(7):1122-1128. doi: 10.1093/ndt/gfx258.

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

Author information

1
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
2
Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.
3
Escuela de Nutrición, Universidad de la República, Montevideo, Uruguay.
4
Research Unit Organ Systems, KU Leuven Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
5
Centro de Nefrología and Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
6
Centre for Molecular and Vascular Biology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
7
R&D Group VitaK, Maastricht University, Maastricht, The Netherlands.

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, 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 m2 (P < 0.001). In 938 participants with baseline eGFR ≥60 mL/min/1.73 m2, the incidence of eGFR <60 mL/min/1.73 m2 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 m2 [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 m2 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.

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