TY - JOUR
T1 - Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)
AU - Haroon, Sabrina
AU - Davenport, Andrew
AU - Ling, Lieng Hsi
AU - Tai, Bee Choo
AU - Teo, Lynette Li San
AU - Schurgers, Leon
AU - Chen, Zhaojin
AU - Shroff, Rukshana
AU - Fischer, Dagmar Christiane
AU - Khatri, Priyanka
AU - Low, Sanmay
AU - Tan, Jia Neng
AU - Chua, Horng Ruey
AU - Teo, Boon Wee
AU - Ong, Ching Ching
AU - Subramanian, Srinivas
AU - Yeo, Xi Er
AU - Wong, Weng Kin
AU - Lau, Titus Wai Leong
N1 - Funding Information:
We are grateful to the National University Health System's Investigational Medicine Unit, Department of Diagnostic Imaging and Cardiovascular Imaging Core Laboratory for their role in the execution of the trial. We thank Nattopharma ASA for providing vitamin K2 for the trial. This work was supported by the National Medical Research Council Singapore. [NMRC/CNIG/1138/2015]. The funder had no role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. Anonymized individual patient data can be requested with data sharing agreement.
Funding Information:
This work was supported by the National Medical Research Council Singapore. [NMRC/CNIG/1138/2015]. The funder had no role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
Funding Information:
LS reports consultancy fee from Immunodiagnostic systems (IDS), outside the submitted work and grants from NattoPharma, Boehringer Ingelheim, and Bayer outside the submitted work. LJS is a shareholder in Coagulation Profile. All the other authors declare no conflict of interest.
Publisher Copyright:
© 2023 International Society of Nephrology
PY - 2023/9
Y1 - 2023/9
N2 - Introduction: Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods: We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 µg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results: Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55–1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34–1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50–1.94). Conclusion: Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.
AB - Introduction: Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods: We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 µg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results: Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55–1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34–1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50–1.94). Conclusion: Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.
KW - aortic augmentation index
KW - carotid-femoral pulse wave velocity
KW - dephosphorylated undercarboxylated MGP
KW - hemodialysis
KW - vascular calcification
KW - vitamin K
U2 - 10.1016/j.ekir.2023.06.011
DO - 10.1016/j.ekir.2023.06.011
M3 - Article
SN - 2468-0249
VL - 8
SP - 1741
EP - 1751
JO - Kidney International Reports
JF - Kidney International Reports
IS - 9
ER -