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Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus

  • Maria FusaroEmail author
  • Maurizio Gallieni
  • Andrea Aghi
  • Maria Antonietta Rizzo
  • Giorgio Iervasi
  • Thomas L. Nickolas
  • Fabrizio Fabris
  • Maria Cristina Mereu
  • Sandro Giannini
  • Stefania Sella
  • Andrea Giusti
  • Annalisa Pitino
  • Graziella D’Arrigo
  • Maurizio Rossini
  • Davide Gatti
  • Maura Ravera
  • Luca Di Lullo
  • Antonio Bellasi
  • Giuliano Brunori
  • Antonio Piccoli
  • Giovanni Tripepi
  • Mario Plebani
Original Article

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.

Keywords

Diabetes mellitus BGP Vitamin K Hemodialysis 

Notes

Acknowledgements

We thank the VIKI Study Investigators, who provided patient clinical care and collected clinical data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This was an observational study conducted at 18 dialysis centers in Italy. All the local ethics committees approved the study, which was conducted according to the regulations in force related to observational studies. Approval dates ranged from July 14, 2008 to October 26, 2009. Patient enrollment took place between November 2008 and November 2009, and follow-up to assess vital status was performed in December 2011.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40620_2019_595_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 KB)

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Copyright information

© Italian Society of Nephrology 2019

Authors and Affiliations

  • Maria Fusaro
    • 1
    • 2
    Email author
  • Maurizio Gallieni
    • 3
  • Andrea Aghi
    • 4
  • Maria Antonietta Rizzo
    • 5
  • Giorgio Iervasi
    • 1
  • Thomas L. Nickolas
    • 6
  • Fabrizio Fabris
    • 4
  • Maria Cristina Mereu
    • 7
  • Sandro Giannini
    • 4
  • Stefania Sella
    • 4
  • Andrea Giusti
    • 8
  • Annalisa Pitino
    • 1
  • Graziella D’Arrigo
    • 9
  • Maurizio Rossini
    • 10
  • Davide Gatti
    • 10
  • Maura Ravera
    • 11
  • Luca Di Lullo
    • 12
  • Antonio Bellasi
    • 13
  • Giuliano Brunori
    • 14
  • Antonio Piccoli
    • 15
  • Giovanni Tripepi
    • 9
  • Mario Plebani
    • 16
  1. 1.National Research Council (CNR), Institute of Clinical Physiology (IFC)PisaItaly
  2. 2.Department of MedicineUniversity of Padova ItalyPaduaItaly
  3. 3.Nephrology and Dialysis Unit, Department of Clinical and Biomedical Sciences ‘Luigi Sacco’University of MilanMilanItaly
  4. 4.Department of Medicine, Clinica Medica 1University of PadovaPaduaItaly
  5. 5.Nephrology and Dialysis UnitOspedale di Circolo di Busto Arsizio, ASST Valle OlonaBusto ArsizioItaly
  6. 6.Division of Nephrology, Department of MedicineColumbia University Medical CenterNew YorkUSA
  7. 7.Nephrologist Independent ResearcherCagliariItaly
  8. 8.Bone Clinic, Dipartimento delle Cure Geriatriche, Ortogeriatria e Riabilitazione, Ospedale GallieraGenoaItaly
  9. 9.Clinical Epidemiology and Physiopathology of Renal Diseases and HypertensionCNR, Institute of Clinical PhysiologyReggio CalabriaItaly
  10. 10.Rheumatology Unit, Department of Medicine, University of Verona and Regional Center for OsteoporosisVeronaItaly
  11. 11.Department of Nephrology and DialysisS. Martino HospitalGenoaItaly
  12. 12.Department of Nephrology and DialysisParodi-Delfino HospitalColleferroItaly
  13. 13.Department of Nephrology and DialysisS. Anna Hospital, ASST LarianaComoItaly
  14. 14.SC Multizonale di Nefrologia e Dialisi, APSSTrentoItaly
  15. 15.Nephrology UnitUniversity of PaduaPaduaItaly
  16. 16.Laboratory Medicine Unit, Department of MedicineUniversity of PadovaPaduaItaly

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