The Role of Vitamin K in Vascular Calcification in Chronic Kidney Disease Patients
Keywords:
Chronic kidney disease, Maintenance hemodialysis, Vitamin K, Matrix γ-carboxyglutamic acid protein, Vascular calcificationAbstract
Vascular calcification is closely associated with the increased cardiovascular mortality rate in chronic kidney disease (CKD) patients and has a high prevalence. However, current treatment options and outcomes are limited. Matrix γ-carboxyglutamic acid protein is a physiological inhibitor of vascular calcification, and its production requires the involvement of vitamin K for physiological activity. Supplementing vitamin K may be an effective treatment for preventing and managing vascular calcification in CKD patients, particularly in maintenance hemodialysis (MHD) patients who may have widespread vitamin K deficiency. This article provides a review of the role of vitamin K in vascular calcification in CKD patients.
References
Górriz JL, Molina P, Cerverón MJ, et al., 2015, Vascular Calcification in Patients with Nondialysis CKD Over 3 Years. Clin J Am Soc Nephrol, 10(4): 654–666. https://doi.org/10.2215/CJN.07450714
El-Maadawy S, Kaartinen MT, Schinke T, et al., 2003, Cartilage Formation and Calcification in Arteries of Mice Lacking Matrix Gla Protein. Connect Tissue Res, 44 Suppl 1: 272–278.
Schulz E, Arfai K, Liu X, et al., 2004, Aortic Calcification and the Risk of Osteoporosis and Fractures. J Clin Endocrinol Metab, 89(9): 4246–4253. https://doi.org/10.1210/jc.2003-030964
Westenfeld R, Krueger T, Schlieper G, et al., 2012, Effect of Vitamin K2 Supplementation on Functional Vitamin K Deficiency in Hemodialysis Patients: A Randomized Trial. Am J Kidney Dis, 59(2): 186–195. https://doi.org/10.1053/j.ajkd.2011.10.041
Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, et al., 2013, Circulating Species of Matrix Gla Protein and the Risk of Vascular Calcification in Healthy Women. Int J Cardiol, 168(6): e168–170. https://doi.org/10.1016/j.ijcard.2013.08.062
Aoun M, Makki M, Azar H, et al., 2017, High Dephosphorylated-Uncarboxylated MGP in Hemodialysis Patients: Risk Factors and Response to Vitamin K2, A Pre-post Intervention Clinical Trial. BMC Nephrol, 18(1): 191. https://doi.org/10.1186/s12882-017-0609-3
Liabeuf S, Bourron O, Olivier B, et al., 2014, Vascular Calcification in Patients with Type 2 Diabetes: The Involvement of Matrix Gla Protein. Cardiovasc Diabetol, 13: 85. https://doi.org/10.1186/1475-2840-13-85. Erratum in Cardiovasc Diabetol, 14: 9. https://doi.org/10.1186/s12933-014-0164-1
Schurgers LJ, Barreto DV, Barreto FC, et al., 2010, The Circulating Inactive Form of Matrix Gla Protein is a Surrogate Marker for Vascular Calcification in Chronic Kidney Disease: A Preliminary Report. Clin J Am Soc Nephrol, 5(4): 568–575. https://doi.org/10.2215/CJN.07081009
Thamratnopkoon S, Susantitaphong P, Tumkosit M, et al., 2017, Correlations of Plasma Desphosphorylated Uncarboxylated Matrix Gla Protein with Vascular Calcification and Vascular Stiffness in Chronic Kidney Disease. Nephron, 135(3): 167–172. https://doi.org/10.1159/000453368
Delanaye P, Krzesinski JM, Warling X, et al., 2014, Dephosphorylated-uncarboxylated Matrix Gla Protein Concentration is Predictive of Vitamin K Status and is Correlated with Vascular Calcification in a Cohort of Hemodialysis Patients. BMC Nephrol, 15: 145. https://doi.org/10.1186/1471-2369-15-145
Meuwese CL, Olauson H, Qureshi AR, et al., 2015, Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease. PLoS One, 10(7): e0132353. https://doi.org/10.1371/journal.pone.0132353
Mendoza FJ, Martinez-Moreno J, Almaden Y, et al., 2011, Effect of Calcium and the Calcimimetic AMG 641 on Matrix-Gla Protein in Vascular Smooth Muscle Cells. Calcif Tissue Int, 88(3): 169–178. https://doi.org/10.1007/s00223-010-9442-4
Kaesler N, Magdeleyns E, Herfs M, et al., 2014, Impaired Vitamin K Recycling in Uremia is Rescued by Vitamin K Supplementation. Kidney Int, 86(2): 286–293. https://doi.org/10.1038/ki.2013.530
Holden RM, Sanfilippo AS, Hopman WM, et al., 2007, Warfarin and Aortic Valve Calcification in Hemodialysis Patients. J Nephrol, 20(4): 417–422.
Ünlü S, Şahinarslan A, Kılıç HK, et al., 2020, Long-Term Vitamin-K Antagonist Use and Coronary Artery Calcification. Herz, 45(6): 580–585. https://doi.org/10.1007/s00059-018-4760-9
Andrews J, Psaltis PJ, Bayturan O, et al., 2018, Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound. JACC Cardiovasc Imaging, 11(9): 1315–1323. https://doi.org/10.1016/j.jcmg.2017.04.010
Brandenburg VM, Cozzolino M, Ketteler M, 2011, Calciphylaxis: A Still Unmet Challenge. J Nephrol, 24(2): 142–148. https://doi.org/10.5301/jn.2011.6366
Hayashi M, Takamatsu I, Kanno Y, et al., 2012, A Case-control Study of Calciphylaxis in Japanese End-stage Renal Disease Patients. Nephrol Dial Transplant, 27(4): 1580–1584. https://doi.org/10.1093/ndt/gfr658
Geleijnse JM, Vermeer C, Grobbee DE, et al., 2004, Dietary Intake of Menaquinone is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. J Nutr, 134(11): 3100–3105. https://doi.org/10.1093/jn/134.11.3100
Brandenburg VM, Reinartz S, Kaesler N, et al., 2017, Slower Progress of Aortic Valve Calcification With Vitamin K Supplementation: Results From a Prospective Interventional Proof-of-Concept Study. Circulation, 135(21): 2081–2083. https://doi.org/10.1161/CIRCULATIONAHA.116.027011. Erratum in Circulation, 141(3): e54. https://doi.org/10.1161/CIR.0000000000000752
El Asmar MS, Naoum JJ, Arbid EJ, 2014, Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation of Vascular Calcification: A Review. Oman Med J, 29(3): 172–177. https://doi.org/10.5001/omj.2014.44
Zwakenberg SR, de Jong PA, Bartstra JW, et al., 2019, The Effect of Menaquinone-7 Supplementation on Vascular Calcification in Patients with Diabetes: A Randomized, Double-blind, Placebo-controlled Trial. Am J Clin Nutr, 110(4): 883–890. https://doi.org/10.1093/ajcn/nqz147
Mansour AG, Hariri E, Daaboul Y, et al., 2017, Vitamin K2 Supplementation and Arterial Stiffness among Renal Transplant Recipients–A Single-arm, Single-center Clinical Trial. J Am Soc Hypertens, 11(9): 589–597. https://doi.org/10.1016/j.jash.2017.07.001
Oikonomaki T, Papasotiriou M, Ntrinias T, et al., 2019, The Effect of Vitamin K2 Supplementation on Vascular Calcification in Haemodialysis Patients: A 1-year Follow-up Randomized Trial. Int Urol Nephrol, 51(11): 2037–2044. https://doi.org/10.1007/s11255-019-02275-2
De Vriese AS, Caluwé R, Pyfferoen L, et al., 2020, Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. J Am Soc Nephrol, 31(1): 186–196. https://doi.org/10.1681/ASN.2019060579. Epub 2019 Nov 8. PMID: 31704740; PMCID: PMC6935010.
Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, et al., 2015, Effect of Vitamin K2 on Progression of Atherosclerosis and Vascular Calcification in Nondialyzed Patients with Chronic Kidney Disease Stages 3–5. Pol Arch Med Wewn, 125(9): 631–640. https://doi.org/10.20452/pamw.3041
Machado AD, Gómez LM, Marchioni DML, et al., 2018, Association between Dietary Intake and Coronary Artery Calcification in Non-Dialysis Chronic Kidney Disease: The PROGREDIR Study. Nutrients, 10(3): 372. https://doi.org/10.3390/nu10030372
Theuwissen E, Cranenburg EC, Knapen MH, et al., 2012, Low-dose Menaquinone-7 Supplementation Improved Extra-hepatic Vitamin K Status, But Had No Effect on Thrombin Generation in Healthy Subjects. Br J Nutr, 108(9): 1652–1657. https://doi.org/10.1017/S0007114511007185