Vitamin K supplementation to improve vascular stiffness in CKD: The K4Kidneys randomized controlled trial

TY - JOUR

T1 - Vitamin K supplementation to improve vascular stiffness in CKD

T2 - The K4Kidneys randomized controlled trial

AU - Witham, Miles

AU - Lees, Jennifer S.

AU - White, Myra

AU - Band, Margaret

AU - Bell, Samira

AU - Chantler, Donna J.

AU - Ford, Ian

AU - Fulton, Roberta

AU - Kennedy, Gwen

AU - Littleford, Roberta

AU - McCrea, Ian V.

AU - McGlynn, Deborah

AU - Panarelli, Maurizio

AU - Ralston, Maximilian R.

AU - Rutherford, Elaine

AU - Severn, Alison

AU - Thomson, Nicola

AU - Traynor, Jamie P.

AU - Struthers, Allan D.

AU - Wetherall, Kirsty

AU - Mark, Patrick B.

N1 - Funding Information: J.S. Lees reports personal fees from AstraZeneca, Bristol-Myers Squibb, and Pfizer, outside the submitted work. P.B. Mark reports personal fees from AstraZeneca, grants from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from Janssen, personal fees and nonfinancial support from Napp, personal fees from Novartis, personal fees from Pfizer, personal fees and nonfinancial support from Pharmacosmos, and personal fees and nonfinancial support from Vifor, outside the submitted work. E. Rutherford reports grants from Chief Scientist Office, outside the submitted work. All remaining authors have nothing to disclose. Funding Information: This work was funded by British Heart Foundation grant PG/14/75/31083 (to P. Mark, A. Struthers, I. Ford, and M. Witham). J. Lees was supported by Kidney Research UK training fellowship TF_013_20161125. E. Rutherford and J. Lees are supported by Chief Scientist Office Scotland Clinical Lectureships. M. Witham acknowledges support from the National Institute for Health Research Newcastle Biomedical Research Centre. Publisher Copyright: Copyright © 2020 by the American Society of Nephrology

PY - 2020/10

Y1 - 2020/10

N2 - 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 m 2). We randomly assigned participants to receive 400 mg 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.

AB - 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 m 2). We randomly assigned participants to receive 400 mg 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.

KW - Vitamin K

KW - Chronic kidney disease

KW - Vascular calcification

KW - Arterial stiffness

UR - https://www.scopus.com/pages/publications/85090234736

U2 - 10.1681/ASN.2020020225

DO - 10.1681/ASN.2020020225

M3 - Article

C2 - 32817311

SN - 1046-6673

VL - 31

SP - 2434

EP - 2445

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

IS - 10

ER -