Vitamin K supplementation and arterial calcification in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial
What this study found
Vitamin K2 supplementation improved vitamin K status but did not significantly slow arterial calcification over 2 years. In the vitamin K arm, serum MK-7 increased progressively and was 40-fold higher than placebo at year 2, while plasma dp-ucMGP was 40-45% lower than placebo and PIVKA-II was lowered by about 45%. Despite these biomarker effects, carotid-femoral PWV, CAC, CVC, and AAC did not differ significantly versus placebo, and calcification progressed in both groups. The adjusted year 2 between-group difference in cfPWV was 1.1 m/s (95% CI -0.1 to 2.2; P = 0.07).
- Study & population
- Double-blind, randomized, placebo-controlled trial in adult patients receiving maintenance dialysis at multiple centers in Denmark.
- Intervention
- Oral vitamin K2 as menaquinone-7 (MK-7), one daily tablet containing 360 mg, taken every morning with some dairy fat for 2 years.
- Key limitation
- The trial was small and had substantial attrition, with marked loss to follow-up by year 2 and very small analyzable samples for imaging outcomes.
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Open PDFOriginal abstract
Abstract 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), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients. Methods In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized 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 aortic calcification (AAC) were used to assess arterial calcification. Results Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, 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% confidence interval (CI) −2029 to −730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI −0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI −554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences. Conclusions Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.