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

Fang Fei Wei; Sander Trenson; Lutgarde Thijs; Qi Fang Huang; Zhen Yu Zhang; Wen Yi Yang; Paula Moliterno; Karel Allegaert; José Boggia; Stefan Janssens; Peter Verhamme; Cees Vermeer; Jan A. Staessen

doi:10.1093/ndt/gfx258

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

Fang Fei Wei, Sander Trenson, Lutgarde Thijs, Qi Fang Huang, Zhen Yu Zhang, Wen Yi Yang, Paula Moliterno, Karel Allegaert, José Boggia, Stefan Janssens, Peter Verhamme, Cees Vermeer^*, Jan A. Staessen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

33 Citations (Scopus)

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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, 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.

Original language	English
Pages (from-to)	1122-1128
Number of pages	7
Journal	Nephrology Dialysis Transplantation
Volume	33
Issue number	7
DOIs	https://doi.org/10.1093/ndt/gfx258
Publication status	Published - Jul 2018
Externally published	Yes

Bibliographical note

Funding Information:
The study was supported by the grants from the European Union (HEALTH-FP7-278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) currently supports the Studies Coordinating Centre in Leuven.

Publisher Copyright:
© 2018 The Author(s).

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Desphospho-uncarboxylated matrix Gla protein is a novelFinal published version, 238 KBLicence: CC BY-NC

Cite this

Wei, F. F., Trenson, S., Thijs, L., Huang, Q. F., Zhang, Z. Y., Yang, W. Y., Moliterno, P., Allegaert, K., Boggia, J., Janssens, S., Verhamme, P., Vermeer, C., & Staessen, J. A. (2018). Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population. Nephrology Dialysis Transplantation, 33(7), 1122-1128. https://doi.org/10.1093/ndt/gfx258

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title = "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, 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, 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.",

author = "Wei, {Fang Fei} and Sander Trenson and Lutgarde Thijs and Huang, {Qi Fang} and Zhang, {Zhen Yu} and Yang, {Wen Yi} and Paula Moliterno and Karel Allegaert and Jos{\'e} Boggia and Stefan Janssens and Peter Verhamme and Cees Vermeer and Staessen, {Jan A.}",

note = "Funding Information: The study was supported by the grants from the European Union (HEALTH-FP7-278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) currently supports the Studies Coordinating Centre in Leuven. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = jul,

doi = "10.1093/ndt/gfx258",

language = "English",

volume = "33",

pages = "1122--1128",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "7",

}

Wei, FF, Trenson, S, Thijs, L, Huang, QF, Zhang, ZY, Yang, WY, Moliterno, P, Allegaert, K, Boggia, J, Janssens, S, Verhamme, P, Vermeer, C & Staessen, JA 2018, 'Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population', Nephrology Dialysis Transplantation, vol. 33, no. 7, pp. 1122-1128. https://doi.org/10.1093/ndt/gfx258

TY - JOUR

T1 - Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population

AU - Wei, Fang Fei

AU - Trenson, Sander

AU - Thijs, Lutgarde

AU - Huang, Qi Fang

AU - Zhang, Zhen Yu

AU - Yang, Wen Yi

AU - Moliterno, Paula

AU - Allegaert, Karel

AU - Boggia, José

AU - Janssens, Stefan

AU - Verhamme, Peter

AU - Vermeer, Cees

AU - Staessen, Jan A.

N1 - Funding Information: The study was supported by the grants from the European Union (HEALTH-FP7-278249-EUMASCARA, HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, G.088013, and 11Z0916N) currently supports the Studies Coordinating Centre in Leuven. Publisher Copyright: © 2018 The Author(s).

PY - 2018/7

Y1 - 2018/7

N2 - 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, 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.

AB - 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, 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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U2 - 10.1093/ndt/gfx258

DO - 10.1093/ndt/gfx258

M3 - Article

C2 - 28992263

AN - SCOPUS:85048834080

SN - 0931-0509

VL - 33

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EP - 1128

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 7

ER -

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

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