Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins (Fusaro M et al)
Matrix Gla protein (MGP) and bone Gla protein (BGP) are two vitamin K-dependent proteins (VKDPs) involved in the regulation of vascular calcification (VC). VC is an important risk factor for cardiovascular morbidity and mortality in chronic kidney disease (CKD). The prevalence of calcification of large arteries has been found to be as high as 60–80% in hemodialysis patients.
Interestingly, a significant association between VC in medium caliber arteries and the rate of prevalent vertebral fractures has been reported in haemodialysis patients . Additionally, both severe VC and vertebral fractures were positively associated with mortality, with a three-fold and five-fold increase in relative risk, respectively, in women.
Fusaro et al carried out a secondary analysis of the VIKI study, an observational study designed to assess the prevalence of vitamin K deficiency in 387 hemodialysis patients, to investigate the effects of ongoing treatment for mineral and bone disorders on bone Gla protein (BGP) and Matrix Gla protein (MGP)levels. MGP BGP are two vitamin K-dependent proteins involved in the regulation of vascular calcification (VC).
The researchers evaluated drug consumption, determined BGP and MGP levels, and verified the presence of any vertebral fractures (VF) and VC by spine radiographs. Total BGP levels were twice as high with calcimimetics versus no calcimimetics (290 vs. 158.5 mcg/L, p < 0.0001) and 69% higher with vitamin D analogs (268 vs. 159 mcg/L, p < 0.0001). Total MGP was 19 % higher with calcimimetics (21.5 vs. 18.1 mcg/L, p = 0.04) and 54 % higher with calcium acetate (27.9 vs. 18.1 mcg/L, p = 0.003); no difference was found with vitamin D analogs (21.1 vs. 18.3 mcg/L, p = 0.43). Median Total BGP level was 29 % lower in patients with ≥1 VF (151 vs. 213 mcg/L, p = 0.0091) and 36 % lower in patients with VC (164 vs. 262.1 mcg/L, p = 0.0003). In non-survivors, median BGP and MGP were lower, but only for MGP this difference reached the statistical significance (152 vs. 191 mcg/L, p = 0.20 and 15.0 vs. 19.7 mcg/L, p = 0.02, respectively).
This study shows that vitamin D analogs and calcimimetics improve VKDP levels. The effects of the individual therapies are partially additive, making the combination most effective.
Authors commented: “Pending studies on vitamin K supplementation, calcimimetics, and vitamin D analogs may play a role in preserving vitamin K-dependent protein activity, thus contributing to bone and vascular health in CKD patients.”
Fusaro M, Giannini S, Gallieni M, Noale M, Tripepi G, Rossini M, Messa P, Rigotti P, Pati T, Barbisoni F, Piccoli A, Aghi A, Alessi M, Bonfante L, Fabris F, Zambon S, Sella S, Iervasi G, Plebani M. Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. Endocrine. 2016 Feb;51(2):333-41. doi: 10.1007/s12020-015-0673-z. Epub 2015 Jul 1.