This post is a summary of a presentation I attended at the National Kidney Foundation Spring Clinical Meeting in New Orleans on May 7, 2026.
Presented by K Sashi Kant
CVD is the main reason patients living with kidney disease diet – so this is one of the most important outcomes.
Objectives:
- Review causes for Vitamin K deficiency
- Carboxylated proteins (vitamin K mediated) essential to bone and vascular health
- Explain my CVD is so prevalent and so poorly managed in chronic HD populations
- Look at both observational and clinical trials in Vitamin K
Black and Hispanic populations are more likely to develop ESKD than white populations
- Does this relate to Vitamin K (this is my question?)
What are the causes of mortality in ESKD?
- Almost 60% of people die due to probable cardiac causes.
- This is a major driver of healthcare costs. ESKD likely costs as much as a trillion dollars annually in the US.
CVD as a % of causes increases as eGFR declines. More pronounced among people on dialysis. But why?
- Could it be related to microvascular, small vessel disease?
- Traditional risk factors for CVD flatten out in CKD – suggesting they aren’t great indicators.
- E.g. Abnormal lipids, smoking, diabetes, older age, etc
- Non-atherosclerotic factors are significant contributes to CVD in this population.
- E.g. Mine bone disorders, uremic toxins, inflammation, oxidative stress
- This may all be related to disordered Vitamin K metabolism.
- E.g. Mine bone disorders, uremic toxins, inflammation, oxidative stress
What are the risk factors of Vitamin K deficiencies?
- Decreased dietary intake (may be related to traditional low K diet recommendations)
- Uremic vitamin K antagonist >> impaired Vitamin K recycling
- Impaired gut microbiome
- Impairs Vitamin K synthesis in the colon
- Increases systemic inflammation and downstream impacts
- Phosphate binders and other medications such as PPIs and statins
All of these result in decreased production of carboxylated matrix proteins.
Where does Vitamin K come from?
- K1 – green leafy vegetables/roasted soybeans
- Has a shorter half life than K2
- Absorbed at 90% in the gut
- But low amounts get through the liver (5%)
- K2 – fermented foods, gut anaerobes
- Menaquinone: Short half life (1.5 hours)
- Menaquinone-7 longer half life (70 hours)
- Lower absorption but better resilience through the liver allowing them to get to the more metabolically active tissues of the body
Vitamin K absorption is increased when had with a fatty meal.
Vitamin K functions within a cycle in the body – but various dietary issues or other inhibitors can result in inefficient production of important proteins and facilitators to catalyse the Vitamin K cycle.
How does warfarin impact the Vitamin K cycle?
Warfarin interrupts the vitamin K cycle to reduce important coagulation proteins.
Summary of Vitamin K protein metabolites
- Activate Bone Gla protein suppresses pro osteoclasts and inhibits osteoclast formation.
- Also dependent on Vitamin D.
- Activate matrix Gla protein: potent inhibitor of calcification.
- Leads to stiffening of the vessels
- Marker of inadequate Vitamin K action
- Vascular smooth muscle cells convert themselves to a bone phenotype
- Also reduces mineralization of the bone
What are the biomarkers of Vitamin K deficiency?
These markers are reliable in both HD and PD. All trend toward normal with MK-7 supplementation
- Increased dp-ucMGP
- Lower plasmas phylloquinone
- Increased ucOC
- Increased PIVKA-11
What are the outcomes of low dp-ucMGP?
- People with low Dp-ucMGP have faster eGFR decline.
- Increases CV mortality in T2DM
- In ESRD patients survival decreases (related to both CV and all cause mortality)
- This was true even when corrected for age, BMI and T2DM status
- The hazard ratio suggested your risk was twice
Is there a relationship between Vitamin K status and calciphylaxis?
Yes. In patients with calciphylaxis, there were significantly higher rates of Vitamin K deficiency, regardless of whether or not people were on warfarin.
Is there a relationship between Vitamin K status and graft survival post kidney transplant?
Yes. Those who were vitamin K deficient showed lower graft survival.
Is there a relationship between Vitamin K status and fracture in ESKD patients?
Yes. Vitamin K deficiency also increases vertebral fractures and calcification in HD patients.
Are both K1 and K2 equally associated with these outcomes?
No. It is the metabolites of K2 that are most associated with these outcomes.
Vitamin K study summary
- In a meta-analysis in healthy post-menopausal women – all studies showed benefit of Vitamin K supplementation on vertebral fractures (reduced risk by ~50%). MK-7 supplementation reduced arterial stiffness in health postmenopausal women
- In people with T2DM but no CKD, 3 and 6 month supplementation of K2 was associated with reductions in FBG and A1C, with increased fasting insulin levels and improved insulin sensitivity.
- In people with aortic valve calcification K1 supplementation as associated with reductions in calcification volume. People who were not given K supplementation showed increased calcification volume during the study duration.
Of note: These studies all used supplementation. These studies don’t tell us how changing dietary intake of Vitamin K may change outcomes.
What about in ESRD patients?
- Vitamin K2 supplementation decreased dp-uc-MGP levels BUT the results were disappointing:
- One study showed that supplementation improved Vitamin K markers didn’t associate with improved clinical outcomes.
- There was also a small study using K1 that may have shown some improvements, but this study was small and the improvements were quite modest.
- Though Vitamin K supplementation is generally considered to be safe in these populations as the rates of adverse events in these studies has been low.
Why are we not seeing as compelling results in ESKD compared to the general population?
- The disease may be too advanced to yield benefit
- Studies are too short
- Blood levels of Vitamin K markers may not be the correct measures
- Study populations are too small
My Summary:
- Vitamin K status is associated with calcification and bone health in the general population
- Most patients living with CKD are deficient in CKD
- There is biological plausibility that Vitamin K status could be a therapy target to help reduce CV outcomes in the CKD population
- But, to date studies on Vitamin K supplementation in ESRD and CKD populations have failed to demonstrate compelling clinical benefit, though studies have been short and small, so this remains an area for further study.
