Vitamin K, vertebral fractures, vascular calcifications and mortality : Vitamin K Italian (VIKI) dialysis study

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones - MKs) is involved in the production of bone and matrix Gla proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification and survival in 387 patients on hemodialysis for ≥1year. We determined plasma levels of vitamin K compound, bone-Gla-protein, matrix-Gla-protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≥20%), aortic and iliac calcifications were also investigated in a spine (D5-L4) radiograph. Three-year patients' survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%) and MK4 (14.5%). 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (OR 2.94 95%CI 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR 2.82 95%CI 1.14-7.01), whereas MK5 deficiency actually protected against it (OR 0.38 95%CI 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR 1.64 95%CI 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR 1.76 95%CI 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification