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Randomized Controlled Trial
. 2020 Oct;31(10):2434-2445.
doi: 10.1681/ASN.2020020225. Epub 2020 Aug 13.

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial

Miles D Witham  1   2 , Jennifer S Lees  3 , Myra White  2 , Margaret Band  4 , Samira Bell  2 , Donna J Chantler  5 , Ian Ford  6 , Roberta L Fulton  7 , Gwen Kennedy  2 , Roberta C Littleford  8 , Ian V McCrea  9 , Deborah McGlynn  10 , Maurizio Panarelli  5 , Maximilian R Ralston  3 , Elaine Rutherford  3 , Alison Severn  11 , Nicola Thomson  10 , Jamie P Traynor  10 , Allan D Struthers  2 , Kirsty Wetherall  6 , Patrick B Mark  3
Affiliations
Randomized Controlled Trial

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial

Miles D Witham et al. J Am Soc Nephrol. 2020 Oct.

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).

Keywords: arterial stiffness; chronic kidney disease; vascular calcification; vitamin K.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials (CONSORT) flow diagram. FAS, full analysis set; Pt, participant.
Figure 2.
Figure 2.
Individual change in dp-ucMGP levels between baseline and 12 month follow-up.
Figure 3.
Figure 3.
Forest plot of vascular stiffness. (A) Results without current trial; (B) results with current trial.
See this image and copyright information in PMC

References

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