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.