Miles D Witham1,2, Jennifer S Lees3, Myra White2, Margaret Band4, Samira Bell2, Donna J Chantler5, Ian Ford6, Roberta L Fulton7, Gwen Kennedy2, Roberta C Littleford8, Ian V McCrea9, Deborah McGlynn10, Maurizio Panarelli5, Maximilian R Ralston3, Elaine Rutherford3, Alison Severn11, Nicola Thomson10, Jamie P Traynor10, Allan D Struthers2, Kirsty Wetherall6, Patrick B Mark3. 1. AGE Research Group, National Institute for Health Research Newcastle Biomedical Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle-upon-Tyne National Health Service Trust, Tyne, United Kingdom Miles.Witham@newcastle.ac.uk. 2. School of Medicine, University of Dundee, Dundee, United Kingdom. 3. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. 4. Tayside Clinical Trials Unit, Ninewells Hospital, Dundee, United Kingdom. 5. Department of Clinical Biochemistry, National Health Service Greater Glasgow and Clyde, Glasgow Royal Infirmary, Glasgow, United Kingdom. 6. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom. 7. School of Nursing and Health Sciences, University of Dundee, Dundee, United Kingdom. 8. University of Queensland, Brisbane, Queensland, Australia. 9. Department of Radiology, National Health Service Greater Glasgow and Clyde, Queen Elizabeth University Hospital, Glasgow, United Kingdom. 10. Clinical Research Facility, National Health Service Greater Glasgow and Clyde, Queen Elizabeth University Hospital, Glasgow, United Kingdom. 11. Renal Unit, National Health Service Tayside, Ninewells Hospital, Dundee, United Kingdom.
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).
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).
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