Background Renal transplant recipients (RTRs) exhibit increased vascular stiffness and calcification; these parameters are associated with increased cardiovascular risk. Activity of endogenous calcification inhibitors such as matrix gla protein (MGP) is dependent on vitamin K. RTRs commonly have subclinical vitamin K deficiency. The Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel Stiffness (ViKTORIES) study assesses whether vitamin K supplementation reduces vascular stiffness and calcification in a diverse population of RTR.
Methods and analysis ViKTORIES (ISRCTN22012044) is a single-centre, phase II, parallel-group, randomised, double-blind, placebo-controlled trial of the effect of vitamin K supplementation in 90 prevalent RTR. Participants are eligible if they have a functioning renal transplant for >1 year. Those on warfarin, with atrial fibrillation, estimated glomerular filtration rate <15 mL/min/1.73 m2 or contraindications to MRI are excluded. Treatment is with vitamin K (menadiol diphosphate) 5 mg three times per week for 1 year or matching placebo. All participants have primary and secondary endpoint measures at 0 and 12 months. The primary endpoint is ascending aortic distensibility on cardiac MR imaging. Secondary endpoints include vascular calcification (coronary artery calcium score by CT), cardiac structure and function on MR, carotid-femoral pulse wave velocity, serum uncarboxylated MGP, transplant function, proteinuria and quality of life. The study is powered to detect 1.0×10–3 mm Hg-1 improvement in ascending aortic distensibility in the vitamin K group relative to placebo at 12 months. Analyses will be conducted as between-group differences at 12 months by intention to treat.
Discussion This trial may identify a novel, inexpensive and low-risk treatment to improve surrogate markers of cardiovascular risk in RTR.
- risk factors
- CT scanning
- clinical trials
- renal disease
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Twitter @jennifer_s_lees, @kenneth_mangion
Contributors JSL, ER, AGJ, MDW and PBM designed the trial. JSL, KB and PBM organised trial approvals and set up. JSL, RW, TH, ER, GR, KM and PBM developed imaging protocols. All authors contributed to and approve this manuscript.
Funding ViKTORIES is an investigator-led clinical trial that is funded by Kidney Research UK (TF_013_20161225) and Darlinda’s Charity for Renal Research. JSL is personally funded by a Kidney Research UK Training Fellowship (TF_013_20161225) and supported by a British Heart Foundation Centre of Excellence Award (RE/13/5/30177).
Competing interests MDW and PBM are investigators on trials of vitamin K supplementation in patients with chronic kidney disease and patients with falls (funded from British Heart Foundation and Chief Scientist Office, Scottish Government).
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. Data will be available through the Virtual International Renal and Transplant Trials Archive (http://www.virtualtrialsarchives.org/virtta/)
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