vitamin-k-1 and Renal-Insufficiency

Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC.. We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies.. The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress.. In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Topics: Animals; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Male; Models, Animal; Phosphates; Rats; Renal Dialysis; Renal Insufficiency; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; X-Ray Microtomography

Intra- and interindividual variation of phylloquinone (vitamin K1) concentrations was investigated by repeat analysis of serum from 28 hemodialysis patients with different apolipoprotein E genotypes. Phylloquinone concentrations ranged from 0.1 to 9.0 nM, with a mean of 1.08 nM (standard deviation 1.90 nM). Most of the variation in serum phylloquinone concentrations was due to differences between patients; the ratio of intra- to interindividual variation was 0.17. Serum triglyceride concentrations and apoE genotype together accounted for 64% of interindividual variation; in contrast, only 6% of intraindividual variation could be attributed to differences in triglyceride concentrations. The small residual variance implies that different phylloquinone consumption levels contributed relatively little to the variation of serum concentrations ( < 36% of interindividual variance). The results suggest that individual disposition is a more important determinant of serum phylloquinone concentrations than dietary phylloquinone intake.

Topics: Aged; Humans; Middle Aged; Renal Dialysis; Renal Insufficiency; Vitamin K 1