WASHINGTON—Vitamin K has shown promising efficacy in the treatment of calciphylaxis, according to the findings of the first randomized placebo-controlled trial of a treatment for this serious medical problem presented at the American Society of Nephrology’s Kidney Week 2019 meeting. No approved medication exists for treating calciphylaxis, a rare and potentially fatal condition that occurs predominantly among patients on dialysis.
In a 12-week phase 2 study that enrolled 26 patients with calciphylaxis, Sagar U. Nigwekar, MD, MMSc, of Massachusetts General Hospital in Boston, and colleagues found that patients treated with oral phytonadione, a form of vitamin K, was associated with a significantly lower mortality rate compared with placebo at 12 weeks (0% vs 31%). In addition, phytonadione-treated patients experienced significant decreases the size of a patient’s largest skin lesion, the combined size of all lesions, and pain intensity compared with placebo.
Previous studies suggested that many patients who experience calciphylaxis had received treatment with warfarin—a vitamin K antagonist. They hypothesized that vitamin K deficiency increases the risk of calciphylaxis through reduced activity of matrix Gla protein (MGP). The protein blocks calcification, but it requires vitamin K for its activation. “So, in patients who are vitamin K deficient or are on treatments such as warfarin, this protein does not remain active, and patients are left with a predisposition for calcification,” Dr Nigwekar told Renal & Urology News. The trial showed that phytonadione significantly decreased levels of inactive MGP. The median change in the level of inactive MGP between baseline and 12 weeks was -1014 pmol/L in the phytonadione group compared with -753 among the placebo recipients.
One of the concerns about using vitamin K therapy was the risk of thrombosis, and one patient in the trial experienced hepatic thrombosis. Dr Nigwekar said this is a safety concern that he and his colleagues will be monitoring in their planned phase 3 trial.
Nigwekar SU, Krinsky S, Thadani RI, et al. Phase 2 trial of phytonadione in calciphylaxis. Presented at the American Society of Nephrology’s Kidney Week 2019 meeting held Nov. 5 to 10 in Washington, DC. Poster TH-PO1188.