Vitamin K supplementation and arterial calcification in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial

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), 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.

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

“…Moreover, the study had a high drop-out rate of 51%, and only 52 patients were ultimately included in the analysis. Similarly, the Effect of Vitamin K2 (MK7) on Cardiovascular and Bone Disease in Dialysis Patients (RenaKvit) RCT [ 87 ] recently reported that daily treatment with 360 μg MK-7 for two years in 21 ESKD patients undergoing either HD or PD failed to show any beneficial effect on aortic stiffness or calcification. The main drawbacks of this study were its small sample size and high drop-out rate; of 641 patients originally assessed, 48 only were enrolled and only 21 ultimately completed the trial.…”

Vitamin K and cardiovascular complications in chronic kidney disease patients

“…MK7 supplementation reduced plasma dp-ucMGP by 17%, 33%, and 46%, respectively. 155 Effects of vitamin K2 on surrogate cardiovascular outcomes have been studied in 4 randomized controlled trials (Table 3 43,126,[156][157][158][159][160] ). A small Polish study in 42 patients with CKD stages 3 to 5 compared 90 mg MK7 together with 10 mg of cholecalciferol with cholecalciferol alone.…”

“…Finally, the RenaKvit trial lowered dp-ucMGP serum levels in dialysis patients by up to 39% via the administration of 360 mg MK7 daily, but failed to observe a significant impact on pulse-wave velocity, coronary artery calcification, or abdominal aortic calcification. 159 A Singaporian ongoing trial also assesses the cardiovascular effects of MK7, 360 mg, given 3 times weekly for a total duration of 18 months to hemodialysis patients. 161 None of the above studies reported any adverse events related to vitamin K supplementation.…”

VItamin K In PEritonial DIAlysis (VIKIPEDIA): Rationale and study protocol for a randomized controlled trial

“…Compared to hemodialysis (HD), patients undergoing peritoneal dialysis (PD) have higher PWV values and wave reflection indices, suggesting a higher CV risk in this population [ 2 ]. Moreover, although several ongoing randomized controlled trials (RCTs) assess various calcification scores as outcomes, we will assess PWV because calcification scores are thought to reflect the final and less dynamic stage of vascular remodeling, whereas PWV might be subjective to change through time [ 3 ]. This is why PWV has served as a potential therapeutic target to ameliorate CV risk in ESKD patients in several trials [ 4 ].…”