Nigwekar SU, Bloch DB, Nazarian RM, Vermeer C, Booth SL, Xu D, Thadhani RI, Malhotra R, et al.
Journal of the American Society of Nephrology : JASN. Date of publication 2017 Jun 1;volume 28(6):1717-1722.
1. J Am Soc Nephrol. 2017 Jun;28(6):1717-1722. doi: 10.1681/ASN.2016060651. Epub
2017 Jan 3.
Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of
Calciphylaxis.
Nigwekar SU(1), Bloch DB(2)(3), Nazarian RM(4), Vermeer C(5), Booth SL(6), Xu
D(7), Thadhani RI(7), Malhotra R(8).
Author information:
(1)Divisions of *Nephrology, snigwekar@mgh.harvard.edu.
(2)Rheumatology, Allergy and Immunology, and.
(3)Anesthesia Center for Critical Care Research, Department of Anesthesia,
Critical Care and Pain Medicine, Massachusetts General Hospital, Boston,
Massachusetts.
(4)Pathology Service, Dermatopathology Unit, Massachusetts General Hospital,
Boston, Massachusetts.
(5)R&D Group VitaK, Biopartner Center Maastricht, Maastricht University,
Maastricht, The Netherlands; and.
(6)Vitamin K Laboratory, Jean Mayer USDA Human Nutrition Research Center on
Aging, Tufts University, Boston, Massachusetts.
(7)Divisions of *Nephrology.
(8)Cardiology, and.
Comment in
J Am Soc Nephrol. 2017 Jun;28(6):1667-1668.
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The
ability of MGP to inhibit calcification requires the activity of a vitamin
K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP
carboxylation influences the risk of calciphylaxis in adult patients receiving
dialysis and examined the effects of vitamin K deficiency on MGP carboxylation.
Our study included 20 patients receiving hemodialysis with calciphylaxis (cases)
and 20 patients receiving hemodialysis without calciphylaxis (controls) matched
for age, sex, race, and warfarin use. Cases had higher plasma levels of
uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However,
the fraction of total MGP that was carboxylated (relative cMGP concentration =
cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02
versus 0.69±0.03, respectively; P=0.003). In patients not taking warfarin, cases
had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in
relative cMGP concentration associated with a more than two-fold increase in
calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP
concentration in multivariable adjusted analyses (β=-8.99; P=0.04). In
conclusion, vitamin K deficiency-mediated reduction in relative cMGP
concentration may have a role in the pathogenesis of calciphylaxis. Whether
vitamin K supplementation can prevent and/or treat calciphylaxis requires further
study.
Copyright © 2017 by the American Society of Nephrology.
DOI: 10.1681/ASN.2016060651
PMCID: PMC5461787
PMID: 28049648 [Indexed for MEDLINE]
