No Cardiovascular Benefit From Vitamin K Supplementation for Chronic Kidney Disease Patients

Miles D. Witham, PhD

Vitamin K supplementation might not be the answer to improving cardiovascular outcomes for patients with chronic kidney disease (CKD).

A team, led by Miles D. Witham, AGE Research Group, National Institute for Health Research Newcastle Biomedical Research Center, determined if vitamin K supplementation could improve arterial stiffness in patients with chronic kidney disease.

Vascular calcification is a risk factor for cardiovascular disease that is common among patients with chronic kidney disease. It is also an independent contributor to increased vascular stiffness and vascular risk in CKD patients.

However, vitamin K, a cofactor for proteins involved in prevention of vascular calcification, might improve arterial stiffness in patients with chronic kidney disease.

The investigators conducted a parallel-group, double-blind, randomized trial in 159 patients at least 18 years old with CKD stage 3b or 4 (eGFR 15–45 ml/min per 1.73 m²) in the modified intention-to-treat analysis.

Each patient was randomly assigned to receive either 400 μg oral vitamin K2 (n = 80) or a matching placebo (n = 79) once daily for a year. The mean age in the study was 66 years old.

The investigators sought primary outcomes of the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months, as well as secondary outcomes of augmentation index, abdominal aortic calcification, blood pressure, physical function, and blood markers of mineral metabolism and vascular health.

The investigators also updated a recently published meta-analysis of trials to include the findings of the study.

Ultimately, the researchers did not find differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function.

Recently, researchers identified trends regarding chronic kidney disease incidence rates throughout all major sociodemographic groups.

A Radboud University Medical Center research team analyzed data from the National Health and Nutrition Examination Surveys for 1988-1994 and every 2 years from 1999-2016 on 54,554 individuals at least 20 years old with information on race and ethnicity, socioeconomic status, and serum creatinine levels.

The age-, sex-, and race/ethnicity-adjusted overall prevalence of stage 3 and 4 chronic kidney disease increased from 3.9% in the 1988-1994 time period to 5.2% in the 2003-2004 (difference, 1.3%; 95% CI, 0.9%-1.7% for change).

This remained relatively stable after 2004 at 5.1% in 2015-2016 (difference, −0.1%; 95% CI, −0.7% to 0.4% for change). The trend in adjusted disease prevalence overall differed substantially based on race/ethnicity (P = 0.009 for interaction).

This is especially true for non-Hispanic white and non-Hispanic black people, where the chronic kidney disease increased between 1988-1994 and 2003-2004 and remained stable thereafter.

For Mexican-American individuals, the prevalence of chronic kidney disease was lower than in any other racial or ethnic group and remained stable between 1988-1994 and 2003-2004. However, the prevalence in this patient group nearly doubled between 2003-2004 and 2015-2016 (difference, 2.1%; 95% CI, 0.9%-3.3% for change) to rates similar to those in other racial or ethnic groups.

While the prevalence of CKD has stabilized in recent years, there is still a need to improve treatment and find ways to prevent comorbidities from occurring.

In the updated meta-analysis, there was no effect of vitamin k supplementation found on vascular stiffness or vascular calcification measures.

“Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD,” the authors wrote.

The study, “Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial,” was published in the Journal of the American Society of Nephrology.