Maria Fusaro1,2, Maurizio Gallieni3, Andrea Aghi4, Maria Antonietta Rizzo5, Giorgio Iervasi6, Thomas L Nickolas7, Fabrizio Fabris4, Maria Cristina Mereu8, Sandro Giannini4, Stefania Sella4, Andrea Giusti9, Annalisa Pitino6, Graziella D'Arrigo10, Maurizio Rossini11, Davide Gatti11, Maura Ravera12, Luca Di Lullo13, Antonio Bellasi14, Giuliano Brunori15, Antonio Piccoli16, Giovanni Tripepi10, Mario Plebani17. 1. National Research Council (CNR), Institute of Clinical Physiology (IFC), Via G. Moruzzi 1, 56124, Pisa, PI, Italy. dante.lucia@libero.it. 2. Department of Medicine, University of Padova Italy, Via Giustiniani 2, 35128, Padua, PD, Italy. dante.lucia@libero.it. 3. Nephrology and Dialysis Unit, Department of Clinical and Biomedical Sciences 'Luigi Sacco', University of Milan, Milan, Italy. 4. Department of Medicine, Clinica Medica 1, University of Padova, Padua, Italy. 5. Nephrology and Dialysis Unit, Ospedale di Circolo di Busto Arsizio, ASST Valle Olona, Busto Arsizio, Italy. 6. National Research Council (CNR), Institute of Clinical Physiology (IFC), Via G. Moruzzi 1, 56124, Pisa, PI, Italy. 7. Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY, USA. 8. Nephrologist Independent Researcher, Cagliari, Italy. 9. Bone Clinic, Dipartimento delle Cure Geriatriche, Ortogeriatria e Riabilitazione, Ospedale Galliera, Genoa, Italy. 10. Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR, Institute of Clinical Physiology, Reggio Calabria, Calabria, Italy. 11. Rheumatology Unit, Department of Medicine, , University of Verona and Regional Center for Osteoporosis, Verona, Italy. 12. Department of Nephrology and Dialysis, S. Martino Hospital, Genoa, Italy. 13. Department of Nephrology and Dialysis, Parodi-Delfino Hospital, Colleferro, Italy. 14. Department of Nephrology and Dialysis, S. Anna Hospital, ASST Lariana, Como, Italy. 15. SC Multizonale di Nefrologia e Dialisi, APSS, Trento, Italy. 16. Nephrology Unit, University of Padua, Padua, Italy. 17. Laboratory Medicine Unit, Department of Medicine, University of Padova, Padua, Italy.
Abstract
BACKGROUND AND AIMS: Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DM patients on HD, compared to HD patients without DM, and their association with vascular and bone disease. METHODS: 387 HD patients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan-Meier. RESULTS: Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabetic patients. In univariate Cox regression analysis, DM patients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13-2.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients. CONCLUSIONS: HD patients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HD patients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway.
BACKGROUND AND AIMS: Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DMpatients on HD, compared to HDpatients without DM, and their association with vascular and bone disease. METHODS: 387 HDpatients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan-Meier. RESULTS:Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabeticpatients. In univariate Cox regression analysis, DMpatients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13-2.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients. CONCLUSIONS:HDpatients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HDpatients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway.
Entities:
Keywords:
BGP; Diabetes mellitus; Hemodialysis; Vitamin K
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