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- Title
Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population.
- Authors
Wei, Fang-Fei; Trenson, Sander; Thijs, Lutgarde; Huang, Qi-Fang; Zhang, Zhen-Yu; Yang, Wen-Yi; Moliterno, Paula; Allegaert, Karel; Boggia, José; Janssens, Stefan
- 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 dpucMGP, usingmultivariable-adjusted analyses. Results. From baseline to follow-up 8.9 years later (median), dp-ucMGP increased by 23.0% whereas eGFR decreased by 4.05mL/min/1.73 m² (P < 0.001). In 938 participants with baseline eGFR ≥60mL/min/1.73 m², the incidence of eGFR <60mL/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 3.15mL/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 <60mL/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.
- Subjects
MATRIX Gla protein; GLOMERULAR filtration rate; ALBUMINURIA; BIOMARKERS; BONE morphogenetic proteins; CROSS-sectional method
- Publication
Nephrology Dialysis Transplantation, 2018, Vol 33, Issue 7, p1122
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfx258