Background: Subclinical vitamin K deficiency increasingly is associated with extraosseous calcification in healthy adults. Nondietary determinants of vitamin K status include apolipoprotein E (apoE) genotype, which may influence vitamin K transport to peripheral tissues.
Methods: Serum phylloquinone concentrations and percentage of uncarboxyated osteocalcin (%ucOC) were measured by means of high-performance liquid chromatography and radioimmunoassay in 142 hemodialysis patients, respectively. ApoE phenotype was determined by means of isoelectric focusing of delipidated serum samples and Western blot analysis. Clinical and laboratory data were obtained by using chart review.
Results: Mean age was 62.6 +/- 14.8 (SD) years. Mean phylloquinone level was 0.99 +/- 1.12 nmol/L; 29% of patients had levels less than 0.4 nmol/L. There was no association between phylloquinone level and %ucOC. There were positive correlations between phylloquinone and total cholesterol (P = 0.017), triglyceride (P = 0.022), and ionized calcium levels (P = 0.019). There was a negative correlation between phylloquinone level and dialysis adequacy (P = 0.002). Mean %ucOC was 51.1% +/- 25.8%, and 93% of subjects had values greater than 20%. There were positive correlations between %ucOC and dialysis vintage (P < 0.001), phosphate level (P < 0.001), parathyroid hormone level (P < 0.001), albumin level (P = 0.035), and ionized calcium level (P = 0.046). Seventeen percent of patients were apoE4. Mean %ucOC was significantly greater in apoE4 carriers compared with all other apoE phenotypes (60.1% +/- 28.4% versus 47.8% +/- 24.4%; P = 0.035). In multiple regression analysis with phylloquinone level forced in, independent predictors of %ucOC were phosphate level, dialysis vintage, parathyroid hormone level, and apoE4.
Conclusion: These data indicate suboptimal vitamin K status in hemodialysis patients, shown by low phylloquinone concentrations and high %ucOC in 29% and 93% of subjects, respectively. The apoE4 allele influences osteocalcin gamma-carboxylation in hemodialysis patients.