Assessment of potential biomarkers of subclinical vitamin K deficiency in patients with end-stage kidney disease

BACKGROUND: A significant proportion of hemodialysis patients have functional, but modifiable, vitamin K deficiency. OBJECTIVE: To determine the correlates of poor vitamin K status in hemodialysis patients. DESIGN: Cross-sectional study. SETTING: Hemodialysis units at Kingston General Hospital and its satellite centres, Ontario, Canada. PATIENTS: Patients undergoing outpatient hemodialysis for end-stage kidney disease. MEASUREMENTS: Serum concentrations of phylloquinone, undercarboxylated prothrombin, also known as protein induced by vitamin K absence or antagonism – factor II (PIVKA-II), and the percentage of undercarboxylated osteocalcin (%ucOC). METHODS: Vitamin K status was determined in fasting blood samples of hemodialysis patients. Bivariate relationships were examined using parametric and non-parametric statistics as appropriate. Multivariable linear regression models were applied to identify predictors of vitamin K status. RESULTS: Among 44 HD patients, criteria for subclinical vitamin K deficiency were met in 13.6% (phylloquinone < 0.4 nmol/L), 51% (%ucOC > 20%) and 90.9% (PIVKA-II > 2.0 nmol/L) of subjects. Phylloquinone levels were positively associated with total cholesterol, triglyceride levels and non-smoking status. Higher %ucOC was associated with increased calcium-phosphate product. Increased PIVKA-II levels were observed with advancing age, reduced dialysis adequacy, lower HDL and a history of coronary artery disease. There were no associations found among the individual biomarkers of vitamin K status. In a multi-variable model, triglycerides were the only significant predictor of phylloquinone levels, while increasing phosphate and decreasing PTH were independent predictors of %ucOC. PIVKA-II levels increased by 0.54 nmol/L for every 10-year increase in age. LIMITATIONS: Observational study; small sample size. CONCLUSIONS: A significant proportion of HD patients met criteria for subclinical vitamin K deficiency. Of the biomarkers measured, PIVKA-II may be superior given its independence of renal function or dyslipidemia, both of which may confound the other vitamin K biomarkers. Studies in patients with ESKD linking biomarkers of vitamin K status to important patient outcomes, including cardiovascular disease, nutritional status and mortality, are required in order to determine the optimal biomarker for evaluating vitamin K status in this particular population.