title: Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins.
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.
authors.affiliation: National Research Council (CNR), Neuroscience Institute, Via Giustiniani, 2, 35128, Padua, Italy. dante.lucia@libero.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Fusaro
authors.affiliation: Department of Medicine, Clinica Medica 1, University of Padua, Padua, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Giannini
authors.affiliation: Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gallieni
authors.affiliation: National Research Council (CNR), Neuroscience Institute, Via Giustiniani, 2, 35128, Padua, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Noale
authors.affiliation: CNR-IFC Pathophysiology of Renal Diseases and Hypertension Unit, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
authors.affiliation: Fondazione Ca' Granda-IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.affiliation: Kidney - Pancreas Transplant Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.affiliation: Nephrology and Dialysis Unit, Hospital of Rovigo, Rovigo, Italy.
authors.forename: Tecla
authors.initials: T
authors.lastname: Pati
authors.affiliation: Nephrology and Dialysis Unit, Hospital of Lodi, Lodi, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barbisoni
authors.affiliation: Nephrology Unit, University of Padua, Padua, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piccoli
authors.affiliation: Nephrology Unit, University of Padua, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Aghi
authors.affiliation: Nephrology Unit, University of Padua, Padua, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Alessi
authors.affiliation: Nephrology Unit, University of Padua, Padua, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Bonfante
authors.affiliation: Department of Medicine, Clinica Medica 1, University of Padua, Padua, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabris
authors.affiliation: Department of Medicine, Clinica Medica 1, University of Padua, Padua, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Zambon
authors.affiliation: Department of Medicine, Clinica Medica 1, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sella
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Iervasi
authors.affiliation: Laboratory Medicine Unit, Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000097:blood*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis; D061205:Vascular Calcification / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D014812:Vitamin K / Q000627:therapeutic use; D000097568:Matrix Gla Protein
chemical_list: D002117:Calcitriol; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D010281:Parathyroid Hormone; D014807:Vitamin D; D014812:Vitamin K; D000097568:Matrix Gla Protein; C104450:25-hydroxyvitamin D
keywords: Biochemical markers of bone turnover; CKD; Matrix mineralization; Vascular calcification; Vitamin K proteins