Vitamin-K-Dependent Protection of the Renal Microvasculature: Histopathological Studies in Normal and Diseased Kidneys

Abstract

Vitamin-K-dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. We recently reported in a multiethnic population study that the estimated glomerular filtration rate, a microvascular trait, decreased and the risk of chronic kidney disease increased with higher circulating levels of inactive dephospho-uncarboxylated MGP, a marker of vitamin K deficiency. These findings highlighted the possibility that vitamin K might have a beneficial effect on the renal microcirculation. To substantiate these epidemiological findings, we undertook a pilot study, in which we stained renal tissue samples obtained by biopsy from 2 healthy kidney donors and 4 patients with nephropathy for carboxylated and uncarboxylated MGP and calcium deposits. Three patients had renal calcifications, which were consistently associated with carboxylated and uncarboxylated MGP. Normal renal tissue was devoid of microcalcifications and staining for carboxylated and uncarboxylated MGP. Pending confirmation in a larger study covering a wider range of renal pathologies, these histopathological findings suggest that MGP might inhibit calcification not only in large arteries, as was known before, but in renal tissue as well, thereby highlighting potentially new avenues for promoting renal health, for instance by vitamin K supplementation.

Keywords: Calcification; Kidney; Matrix Gla protein; Microcirculation; Vitamin K.

Fig. 1

Staining of skin microvessels. Arrows refer to the positive staining. Microvascular calcifications (black: von Kossa staining) co-localize with MGP; ucMGP and cMGP indicate uncarboxylated (inactive: dark red) and carboxylated (active: pink) MGP.

Fig. 2

Histopathological findings in a healthy donor and a patient with interstitial nephritis. Tissue samples (magnification ×100) were stained with hematoxylin and eosin (HE), conformation-specific antibodies directed against cMGP and ucMGP matrix Gla protein and for calcium deposits (von Kossa staining). Black arrows point to glomeruli and blue arrows to a microvessel. Healthy donor tissue was negative for calcification, cMGP and ucMGP. Tissue from the patient with interstitial nephritis revealed calcium deposits (black: von Kossa staining), which co-localized with cMGP and ucMGP.