TY - JOUR

T1 - No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency

T2 - A One-Year Randomized, Placebo-Controlled Study

AU - Bladbjerg, Else Marie

AU - Levy-Schousboe, Karin

AU - Frimodt-Møller, Marie

AU - Kjærgaard, Krista D.

AU - Strandhave, Charlotte

AU - Brasen, Claus L.

AU - Frandsen, Niels Erik

AU - Hansen, Ditte

AU - Marckmann, Peter

N1 - Funding Information: Financial Disclosure: Reagents for plasma analyses were funded by Department of Clinical Biochemistry, Esbjerg Hospital, University Hospital of Southern Denmark. The RenaKvit study was funded by The Danish Society of Nephrology, The Danish Kidney Association, The Region Zealand Research Foundation, Kappa Bioscience AS, Aase and Ejnar Danielsens Foundation, Helen and Ejnar Bjørnows Foundation, The Beckett Foundation, and Karen Elise Jensens Foundation. Kappa Bioscience AS and Orkla Care AS donated study tablets, but neither had further part in the study nor any part in interpreting the data or acceptance of the results. Funding Information: KLS’ salary was partially funded by Kappa Bioscience AS, the Danish Society of Nephrology, and the Karen Elise Jensen’s Foundation during the RenaKvit trial. The other authors have nothing to declare. Funding Information: Financial Disclosure: Reagents for plasma analyses were funded by Department of Clinical Biochemistry, Esbjerg Hospital, University Hospital of Southern Denmark. The RenaKvit study was funded by The Danish Society of Nephrology , The Danish Kidney Association, The Region Zealand Research Foundation, Kappa Bioscience AS, Aase and Ejnar Danielsens Foundation, Helen and Ejnar Bjørnows Foundation, The Beckett Foundation, and Karen Elise Jensens Foundation. Kappa Bioscience AS and Orkla Care AS donated study tablets, but neither had further part in the study nor any part in interpreting the data or acceptance of the results. Publisher Copyright: © 2023 National Kidney Foundation, Inc.

PY - 2024

Y1 - 2024

N2 - 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. 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, 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 and serious adverse events 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 <.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 =.04), and no between-group differences in adverse events and serious adverse events. 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.

AB - 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. 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, 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 and serious adverse events 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 <.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 =.04), and no between-group differences in adverse events and serious adverse events. 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.

KW - Biomarkers

KW - chronic kidney disease

KW - dialysis

KW - menaquione-7

KW - thrombin generation

KW - thrombosis

U2 - 10.1053/j.jrn.2023.11.007

DO - 10.1053/j.jrn.2023.11.007

M3 - Journal article

C2 - 38128853

AN - SCOPUS:85181969191

JO - Journal of Renal Nutrition

JF - Journal of Renal Nutrition

SN - 1051-2276

ER -