Calciphylaxis Linked to Low Vitamin K

An enzyme that inhibits vascular calcification depends on the vitamin for conversion to its active form.
An enzyme that inhibits vascular calcification depends on the vitamin for conversion to its active form.

Vitamin K deficiency may have a role in the development of calciphylaxis, a rare but frequently fatal condition in dialysis patients, according to newly published study findings.

The vitamin is an essential cofactor on which gamma-glutamylcarboxylase depends to convert inactive uncarboxylated matrix gla protein (ucMGP) to its active carboxylated form (cMGP), a potent inhibitor of vascular calcification. In a study comparing 20 hemodialysis (HD) patients with calciphylaxis (cases) and a group of 20 HD patients without calciphylaxis matched by age, sex, race, and warfarin use (controls), a team led by Sagar U. Nigwekar, MD, of Massachusetts General Hospital in Boston, found that the fraction of total MGP that was carboxylated was significantly lower in cases than controls (0.58 vs 0.69). Each 0.1 unit reduction in relative cMGP concentration was associated with a greater than 2-fold increased risk of calciphylaxis, Dr Nigwekar and his colleagues reported online ahead of print in Journal of the American Society of Nephrology. In multivariable analysis, vitamin K deficiency was associated with lower relative cMGP concentration.

“Calciphylaxis is a devastating disease with limited understanding of its pathogenesis and no effective treatment,” Dr Nigwekar told Renal & Urology News. “Our present study links vitamin K deficiency with the development of calciphylaxis. This study also identifies matrix gla protein, a vitamin K dependent protein, as a target for future strategies to prevent and/or treat calciphylaxis. We and others have previously reported that warfarin, a vitamin K antagonist, is a risk factor for calciphylaxis. The present study provides biological explanation for that association as we demonstrate impaired activity of matrix gla protein in patients with calciphylaxis.”

The investigators acknowledged that, because of their study's small sample size, confirmation of their findings in larger case-control studies is needed.

Reference

1. Nigwekar SU, Bloch DB, Nazarian RM, et al. Vitamin K-dependent carboxylation of matrix gla protein influences the risk of calciphylaxis. J Am Soc Nephrology 2017; published online ahead of print.

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