How does vitamin K affect left ventricular (LV) function in patients with a history of kidney disease, particularly those with chronic kidney disease (CKD) or end-stage renal disease (ESRD)?

Vitamin K and Left Ventricular Function in CKD/ESRD Patients

Current evidence does not support vitamin K supplementation to improve left ventricular function in patients with chronic kidney disease or end-stage renal disease, and vitamin K should be absolutely avoided in any patient receiving warfarin anticoagulation. 1, 2

Critical Contraindication

• Patients on warfarin or other vitamin K antagonists must never receive vitamin K supplements, as this directly interferes with anticoagulant efficacy. 1, 2
• This contraindication applies across all CKD stages (1-5D) and post-transplantation patients. 1

Evidence on Vitamin K and Cardiovascular Outcomes in CKD

Lack of Clinical Benefit on Vascular Function

• The K4Kidneys randomized controlled trial (2020) found no improvement in pulse wave velocity, augmentation index, blood pressure, B-type natriuretic peptide, or physical function after 12 months of vitamin K2 (400 μg daily) supplementation in 159 patients with CKD stage 3b-4. 3
• A meta-analysis including this trial showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures in CKD patients. 3
• Multiple recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and hemodialysis have consistently failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment. 4

Epidemiological Associations vs. Intervention Outcomes

• While vitamin K deficiency (measured by elevated dephospho-uncarboxylated matrix gla protein [dp-ucMGP] ≥450 pmol/L or low plasma phylloquinone <0.50 nmol/L) was associated with 21-29% higher all-cause mortality risk in the Chronic Renal Insufficiency Cohort study, there was no significant association with atherosclerotic cardiovascular disease events. 5
• This epidemiological association does not translate to clinical benefit from supplementation, as demonstrated by negative intervention trials. 3, 4

Left Ventricular Dysfunction in CKD: The Real Problem

Prevalence and Progression

• Left ventricular hypertrophy (LVH) affects approximately 30% of patients with mild renal insufficiency (creatinine clearance 50-75 mL/min) and increases to 75% by dialysis initiation. 1
• LVH and left ventricular dysfunction develop early in CKD progression, driven by hemodynamic factors, volume overload, and chronic activation of the renin-angiotensin-aldosterone system. 1

Established Management Strategies

• Standard heart failure treatments (ACE inhibitors, beta-blockers, diuretics) should be delivered to CKD patients with close monitoring of GFR and potassium levels. 1
• BNP/NT-proBNP levels are strongly associated with left ventricular hypertrophy and dysfunction in CKD populations, though they must be interpreted with caution relative to GFR as they are inversely associated with kidney function. 1
• Increased vigilance is required when using dual RAAS blockade due to risks of hyperkalemia and acute kidney injury. 1

Clinical Algorithm for Vitamin K Considerations in CKD

Step 1: Anticoagulation Status

• If on warfarin → Absolute contraindication to vitamin K supplementation 1, 2
• If not anticoagulated → Proceed to Step 2

Step 2: CKD Stage Assessment

• CKD Stage 3a-4: Vitamin K2 supplementation may be considered but has no proven benefit for cardiovascular or LV function outcomes 2, 3
• CKD Stage 5D (dialysis): Avoid routine vitamin K supplementation; renal-specific multivitamins typically exclude vitamin K 6

Step 3: Focus on Proven Interventions

• Optimize volume status and achieve dry weight 1
• Implement standard heart failure therapies with appropriate dose adjustments for renal function 1
• Monitor and manage anemia, mineral bone disease, and metabolic acidosis 1
• Assess for and treat coronary artery disease using standard diagnostic approaches 1

Common Pitfalls to Avoid

• Do not supplement vitamin K in any patient on warfarin—this is the most critical error to avoid. 1, 2
• Do not assume vitamin K supplementation will improve cardiovascular outcomes or LV function based on epidemiological associations alone—randomized trials have consistently shown no benefit. 3, 4
• Do not attribute elevated cardiac biomarkers (troponin, BNP) solely to reduced kidney function without clinical context and trend evaluation, as these markers reflect true cardiac pathology including LV dysfunction even in CKD. 1
• Do not delay implementation of proven heart failure therapies while pursuing unproven interventions like vitamin K supplementation. 1

Monitoring Recommendations

• For CKD stage 3 patients, laboratory evaluations should occur every 6-12 months, including assessment of calcium, phosphate, PTH, and 25(OH)D. 2
• Standard CKD monitoring protocols should guide follow-up rather than specific vitamin K-related parameters. 2