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The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients

  • Branislav ApostolovićEmail author
  • Tatjana Cvetković
  • Nikola Stefanović
  • Svetlana Apostolović
  • Marija Anđelković Apostolović
  • Branka Mitić
  • Radmila Veličković Radovanović
  • Karolina Paunović
  • Aleksandra Ignjatović
  • Mina Cvetković
  • Nataša Stević
  • Dusica Pavlović
Nephrology - Original Paper
  • 18 Downloads

Abstract

Purpose

Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral–bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme.

Materials and methods

Patients (n = 142) were genotyped for G-395A Klotho gene. Components of mineral–bone metabolism, classical and non-classical (FGF23, Klotho and vitamin D) as well as echocardiographic examination were determined. Predictive models were designed to determine the significance of Klotho gene variations and mineral–bone metabolism components for left ventricle hypertrophy (LVH).

Results

A-allele carriers were longer on haemodialysis (p = 0.033), and had higher phosphorus levels (p = 0.016) while the level of Klotho protein was significantly lower (p = 0.001) compared to non-A-allele carriers. The best gains were achieved upon addition of allele A, and all three new markers; the AUC made significant improvement from 0.596 to 0.806 (p < 0.001), and improved net reclassification for 82.1% (95% CI 42.9–121.3%).

Conclusions

The genetic background of A-allele carriers of the G-395A Klotho gene polymorphism increases the susceptibility patients to haemodialysis. A-allele carriers are at a higher risk for the development of cardiovascular complications. The addition of non-classical to classical mineral metabolism components improves prediction power to LVH.

Keywords

Klotho gene polymorphism FGF23 Klotho LVH Haemodialysis Predictive models 

Notes

Acknowledgements

This study was supported by the research grant from the Ministry of Education, Science and Technological Development, Republic of Serbia—Project Number 41018.

Compliance with ethical standards

Conflict of interest

The authors report no declarations of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Branislav Apostolović
    • 1
    • 2
    Email author
  • Tatjana Cvetković
    • 1
    • 2
  • Nikola Stefanović
    • 1
  • Svetlana Apostolović
    • 1
    • 4
  • Marija Anđelković Apostolović
    • 1
    • 3
  • Branka Mitić
    • 1
    • 2
  • Radmila Veličković Radovanović
    • 1
    • 2
  • Karolina Paunović
    • 2
  • Aleksandra Ignjatović
    • 1
    • 3
  • Mina Cvetković
    • 1
    • 2
  • Nataša Stević
    • 1
  • Dusica Pavlović
    • 1
  1. 1.Faculty of MedicineUniversity of NišNišSerbia
  2. 2.Clinic of NephrologyClinical Center NišNišSerbia
  3. 3.Department of StatisticsPublic Health Institute NišNišSerbia
  4. 4.Clinic for Cardiovascular DiseasesClinical Centre NišNišSerbia

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