No detectable coagulation activation after vitamin K (MK-7) supplementation in patients on dialysis with functional vitamin K deficiency: a one-year randomized, placebo-controlled study.

OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis.

DESIGN AND METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 μg/daily, n=61) or placebo (n=62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential (ETP), peak thrombin concentration, time to peak, and lag time), clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X, prothrombin fragment 1+2 (F1+2), and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events (AE) and serious adverse events (SAE) were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's Exact test or Pearson's Chi-Squared test.

RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (p<0.001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (p=0.04), and no between-group differences in AE and SAE.

CONCLUSION: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.