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

J Am Soc Nephrol. 2020 Oct;31(10):2434-2445. doi: 10.1681/ASN.2020020225. Epub 2020 Aug 13.


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 (

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

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Dietary Supplements*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulse Wave Analysis
  • Renal Insufficiency, Chronic / complications*
  • Treatment Outcome
  • Vascular Calcification / diagnosis
  • Vascular Calcification / etiology
  • Vascular Calcification / prevention & control*
  • Vascular Stiffness / drug effects*
  • Vitamin K 2 / therapeutic use*
  • Vitamins / therapeutic use*


  • Vitamins
  • Vitamin K 2

Associated data

  • ISRCTN/ISRCTN21444964