Abstract
Matrix Gla protein (MGP) and bone Gla protein (BGP) are two vitamin K-dependent proteins (VKDPs) involved in the regulation of vascular calcification (VC). We carried out a secondary analysis of the VIKI study to evaluate associations between drug consumption and VKDP levels in 387 hemodialyzed patients. The VIKI study assessed the prevalence of vitamin K deficiency in hemodialysis patients. We 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). 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.
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Acknowledgments
We thank the VIKI Dialysis Study Investigators, who provided patient clinical care and collected clinical data. They were the following: MT Vilei, MC Tineo, M. Rebeschini, A. Naso (Padua), C. Grimaldi, A. Mannarino (Florence), D. Ciurlino, S. Bertoli (Sesto San Giovanni, Milan), R. Puggia, A. Caberlotto, S. Mastrosimone, C. Cascone (Treviso), R. Corradini, M. Avolio, B. Giacon (Bolzano), A. Foschi, C. Barbieri, F. Milanesi (Voghera), A. Pica, C. Venturelli, G. Brunori (Trento), T. Pati, A. Gemelli, A.M. Bernardi (Rovigo), F. Barbisoni, A. Elli (Lodi), P. Morachiello, M. Feriani (Mestre), F. Stoppa (Adria), G. Tarroni, E. De Paoli Vitali (Belluno), S. Lucatello, G. Meneghel (Dolo), A. Vianello, F. Antonucci (Feltre, Belluno), V. Pellanda, R. Dell’Aquila (Bassano del Grappa), A. Ferraro, M. De Luca (Castelfranco Veneto, Padua), F.M. Magonara, M. Axia (Schio), M. Spinello, M. Urso (Chioggia, Venice). We also thank Jennifer S Hartwig, MD, medical writer, for editing the manuscript. Availability/disclosure of materials and methods and author access to data: the CNR was the coordinating center; the complete clinical trial archive is there and the statistical analysis was performed there. MF and MN had full access to all the raw data and made them available to the other authors, as appropriate. Any requests regarding clinical or radiographic data should be addressed to MF. Requests regarding laboratory data and laboratory methods should be addressed to MP in Padua (vitamin D and Gla proteins).
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M.F. has received grants from Boehringer Ingelheim, AbbVie, Amgen and Fresenius. SG has received grants from MSD, Abiogen and Amgen. Maurizio Gallieni: In the past 5 years, travel support for participation to meetings and speaking honoraria from Abbvie, Amgen, Genzyme. PM has received grants from AbbVie, Amgen, Fresenius, and Roche. PR has received research grants from Novartis and has participated to advisory boards with Novartis, Astellas, and Chiesi. F.F. has received lectures fees from Bayer, GSK, and Amgen. M.N., G.T., M.R., T.P., F.B., A.P., A.A., M.A., L.B., S.Z., S.S., G.I., and M.P. have no interests to disclose.
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Fusaro, M., Giannini, S., Gallieni, M. et al. Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. Endocrine 51, 333–341 (2016). https://doi.org/10.1007/s12020-015-0673-z
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DOI: https://doi.org/10.1007/s12020-015-0673-z