Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)

Sabrina Haroon; Andrew Davenport; Lieng-Hsi Ling; Bee-Choo Tai; Lynette-Li-San Teo; Leon Schurgers; Zhaojin Chen; Rukshana Shroff; Dagmar-Christiane Fischer; Priyanka Khatri; Sanmay Low; Jia-Neng Tan; Horng-Ruey Chua; Boon-Wee Teo; Ching-Ching Ong; Srinivas Subramanian; Xi-Er Yeo; Weng-Kin Wong; Titus-Wai-Leong Lau

doi:10.1016/j.ekir.2023.06.011

Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK)

Kidney Int Rep. 2023 Jun 22;8(9):1741-1751. doi: 10.1016/j.ekir.2023.06.011. eCollection 2023 Sep.

Authors

Sabrina Haroon¹, Andrew Davenport², Lieng-Hsi Ling³, Bee-Choo Tai⁴, Lynette-Li-San Teo⁵, Leon Schurgers⁶, Zhaojin Chen^{4

7}, Rukshana Shroff⁸, Dagmar-Christiane Fischer⁹, Priyanka Khatri¹, Sanmay Low¹, Jia-Neng Tan¹, Horng-Ruey Chua¹, Boon-Wee Teo¹, Ching-Ching Ong⁵, Srinivas Subramanian¹, Xi-Er Yeo¹, Weng-Kin Wong¹, Titus-Wai-Leong Lau¹

Affiliations

¹ Division of Nephrology, University Medicine Cluster, National University Hospital Singapore, Singapore.
² University College London Center for Nephrology, Royal Free Hospital, University College London, UK.
³ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁴ Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore.
⁵ Department of Diagnostic Imaging, National University Hospital, Singapore.
⁶ Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands.
⁷ Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁸ UCL Great Ormond Street Hospital for Children NHS Foundation Trust, and Institute of Child Health, London, UK.
⁹ Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.

Abstract

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.

Keywords: aortic augmentation index; carotid-femoral pulse wave velocity; dephosphorylated undercarboxylated MGP; hemodialysis; vascular calcification; vitamin K.