Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies

Fang-Fei Wei,Nadja E.A Drummen,Aletta E Schutte,Lutgarde Thijs,Lotte Jacobs,Thibaut Petit,Wen-Yi Yang,Wayne Smith,Zhen-Yu Zhang,Yu-Mei Gu,Tatiana Kuznetsova,Peter Verhamme,Karel Allegaert,Rudolph Schutte,Evelyne Lerut,Pieter Evenepoel,Cees Vermeer,Jan A Staessen

doi:10.1016/j.ebiom.2016.01.011

Fang-Fei Wei, Nadja E.A Drummen + Show 16 more

Open Access

https://doi.org/10.1016/j.ebiom.2016.01.011

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Abstract

BackgroundFollowing activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but its role in preserving renal function remains unknown. MethodsIn 1166 white Flemish (mean age, 38.2years) and 714 South Africans (49.2% black; 40.6years), we correlated estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD [KDOQI stages 2–3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear and logistic regression. ResultsAmong Flemish and white and black Africans, between-group differences in eGFR (90, 100 and 122mL/min/1.73m2), dp-ucMGP (3.7, 6.5 and 3.2μg/L), and CKD prevalence (53.5, 28.7 and 10.5%) were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P≥0.075). For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P=0.023), 1.0 (P=0.56), 2.8 (P=0.0012) and 2.1 (P<0.0001) mL/min/1.73m2 in Flemish, white Africans, black Africans and all participants combined; the odds ratios for moving up one CKD stage were 1.17 (P=0.033), 1.03 (P=0.87), 1.29 (P=0.12) and 1.17 (P=0.011), respectively. InterpretationIn the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health.

Highlights

Vascular smooth muscle cells synthesize matrix Gla protein (MGP), a small secretory protein (11 kD), which contains five γ-carboxyglutamate (Gla) amino-acid residues (Hackeng et al, 2001)
Total uncarboxylated MGP (t-ucMGP), in contrast to dp-ucMGP, is not a marker of vitamin K status, but reflects arterial calcification, lower values being associated with more widespread calcium deposits (Cranenburg et al, 2009; Schurgers et al, 2005)
We investigated our hypothesis in white people enrolled in the FLEMENGHO study (Liu et al, 2015) and sought replication in the white and black participants enrolled in the South African Study Regarding the Influence of Sex, Age and Ethnicity on Insulin Sensitivity and Cardiovascular Function (SAfrEIC) (Kruger et al, 2012)

Summary

Introduction

Vascular smooth muscle cells synthesize matrix Gla protein (MGP), a small secretory protein (11 kD), which contains five γ-carboxyglutamate (Gla) amino-acid residues (Hackeng et al, 2001). In patients with diabetes (Dalmeijer et al, 2013), renal dysfunction, (Schurgers et al, 2010) or macrovascular disease (Mayer et al, 2014), inactive desphospho-uncarboxylated MGP (dp-ucMGP) behaves as a circulating biomarker associated with cardiovascular risk (Dalmeijer et al, 2013), more severe vascular illness (Schurgers et al, 2010), and higher mortality (Mayer et al, 2014). Total uncarboxylated MGP (t-ucMGP), in contrast to dp-ucMGP, is not a marker of vitamin K status, but reflects arterial calcification, lower values being associated with more widespread calcium deposits (Cranenburg et al, 2009; Schurgers et al, 2005). Interpretation: In the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health

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