Background Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla-protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), is prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated if vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients. Methods In a two-year double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomised to vitamin K (menaquinone-7 (MK-7), 360 µg daily), or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aorta calcification (AAC) were used to assess arterial calcification. Results Thirty-seven participants completed year one, 21 completed year two. At year two, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo (mean dp-ucMGP difference: -1380 pmol/L (95% CI: -2029;-730)). There was no significant effect of vitamin K supplementation on cfPWV (mean difference at year two: 1.2 m/s (95% CI: -0.1; 2.4)). CAC Agatston score increased significantly in vitamin K supplemented participants, but not significantly different from placebo (mean difference at year two: 664 (95% CI: -554; 1881)). AAC scores increased in both groups, significantly so within the placebo group at year 1, but with no significant between-group differences. Conclusion Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

Background Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis. Methods In a multicenter double-blind placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultra-distal, and total), femoral neck, lumbar spine (L1-L4), and whole body was assessed by Dual-energy X-ray Absorptiometry. Serum levels of vitamin K1 and MK-7, and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein, and Protein Induced by Vitamin K Absence-II were measured to assess vitamin K status. Results After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation (mean difference of changes relative to placebo -0.023 (95% CI (-0.039;-0.008)) g/cm2), whereas the decrease in lumbar spine BMD seen in the placebo group was prevented (mean difference of changes between groups 0.050 (95% CI (0.015;0.085)) g/cm2. No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7 supplemented participants. Conclusion Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis.

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