Vitamin K supplementation to improve vascular stiffness in chronic kidney disease: the K4Kidneys randomised controlled trial

Witham, M. D. et al. (2020) Vitamin K supplementation to improve vascular stiffness in chronic kidney disease: the K4Kidneys randomised controlled trial. Journal of the American Society of Nephrology, 31(10), pp. 2434-2445. (doi: 10.1681/ASN.2020020225) (PMID:32817311)

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Abstract

BACKGROUND:Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS:To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS:We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS:Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wetherall, Miss Kirsty and Rutherford, Dr Elaine and Mark, Professor Patrick and Lees, Jennifer and Ralston, Dr Maximilian and Ford, Professor Ian and Traynor, Dr Jamie
Authors: Witham, M. D., Lees, J. S., White, M., Band, M., Bell, S., Chantler, D. J., Ford, I., Fulton, R. L., Kennedy, G., Littleford, R. C., McCrea, I. V., McGlynn, D., Panarelli, M., Ralston, M. R., Rutherford, E., Severn, A., Thomson, N., Traynor, J. P., Struthers, A. D., Wetherall, K., and Mark, P. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
ISSN:1046-6673
ISSN (Online):1533-3450
Published Online:13 August 2020
Copyright Holders:Copyright © 2020 by the American Society of Nephrology
First Published:First published in Journal of the American Society of Nephrology 31(10):2434-2445
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172255Vitamin K therapy to improve vascular health in patients with Chronic Kidney Disease - a randomised controlled trialIan FordBritish Heart Foundation (BHF)(218.807844) Vicki GilberInstitute of Cardiovascular & Medical Sciences
300923Vitamin K in Transplanted Kidney Organ Recipients: Investigating vEssel Stiffness (ViKTORIES)Jennifer LeesKidney Research UK (KIDNEYRE)TF_013_20161125CAMS - Cardiovascular Science