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

• In Flemish, eGFR was inversely associated with dp-ucMGP and positively with t-ucMGP.
• In Flemish, the risk of chronic kidney disease increased with higher dp-ucMGP.
• We confirmed the inverse association of eGFR with dp-ucMGP in black South Africans.In a multi-ethnic population study, we assessed the association of renal glomerular filtration, a microvascular trait, with circulating matrix Gla protein (MGP). In white Flemish and in South African blacks, glomerular filtration decreased and the risk of chronic kidney disease increased with higher levels of inactive desphospho-uncarboxylated MGP. Our findings support the notion that following vitamin-K dependent carboxylation active MGP not only inhibits calcification of large arteries, as was known before, but also protects the renal microcirculation. Future studies might test whether vitamin K supplementation promotes renal health in the general population.

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, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), 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 122 mL/min/1.73 m2), dp-ucMGP (3.7, 6.5 and 3.2 μg/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/1.73 m2 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.