title: Assessment of potential biomarkers of subclinical vitamin K deficiency in patients with end-stage kidney disease.
abstract: 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.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Hemodialysis units at Kingston General Hospital and its satellite centres, Ontario, Canada.
  
  
  METHODS
  Patients undergoing outpatient hemodialysis for end-stage kidney disease.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB Canada ; Division of Nephrology, Foothills Medical Centre, 1403 29th Street NW, T2N 2T9 Calgary, AB Canada.
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Elliott
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center of Aging at Tufts University, Boston, MA USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.affiliation: Clinical Research Centre, Kingston General Hospital, Kingston, ON Canada.
authors.forename: Wilma M
authors.initials: WM
authors.lastname: Hopman
authors.affiliation: Division of Nephrology, Department of Medicine, Queen's University, Kingston, ON Canada.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Holden
keywords: Chronic kidney disease; Hemodialysis; Osteocalcin; PIVKA; Phylloquinone; Vitamin K