Preliminary studies in humans with CKD demonstrated that dp-ucMGP levels rise progressively with the severity of CKD [11]. Further, the dp-ucMGP levels were independently associated with aortic calcification measured by abdominal CT as well as mortality over a median duration of follow-up of 846 days [11,32]. These studies support an influence of vitamin K status on calcification in this population. However, whether the carboxylation status of MGP in the circulation represents a surrogate marker for vascular calcification in CKD (i.e., higher ucMGP:cMGP ratio) cannot be determined from these studies. Westenfeld et al., have reported that levels of dp-ucMGP are sensitive to vitamin K2 (e.g., MK-7) supplementation in maintenance HD patients [5]. Whether or not improved vitamin K status translates into a reduction in vascular calcification is still unknown.

Warfarin is a vitamin K antagonist and its use represents a model of vitamin K insufficiency. We have demonstrated that long-term treatment with a vitamin K antagonist, warfarin, is independently associated with greater severity of aortic valve calcification in maintenance HD patients [34]. In addition, warfarin has been anecdotally linked to calciphylaxis in HD patients.