Povezanost varijacija u genu za Klotho protein, parametara mineralno-koštanog metabolizma i ehokardiografskih karakteristika kod bolesnika na hemodijalizi
Докторанд
Apostolović, BranislavМентор
Cvetković, TatjanaЧланови комисије
Mitić, BrankaApostolović, Svetlana
Stefanović, Nikola Z.
Метаподаци
Приказ свих података о дисертацијиСажетак
Mineral bone metabolism disorder plays a major role in the etiopathogenesis of
cardiovascular events in hemodialysis patients. In recent years, many new
parameters associated with the homeostasis of mineral bone metabolisms, such as
fibroblast growth factor 23 (FGF23) and Klotho protein, have been discovered. The
main goal of this study is to discover interrelationships between Klotho protein gene
variations, mineral bone metabolism, and left ventricular hypertrophy (LVH) in
hemodialysis patients.
The study included 142 patients who were genotyped for G-395A and C1818T
Klotho gene polymorphism. Laboratory analyses were performed for routine
parameters of mineral bone metabolism (calcium, phosphorus, parathyroid
hormone, and alkaline phosphatase) and new parameters (FGF23, Klotho, and
vitamin D) and echocardiographic examination. Models for the determination of
predictive capabilities of Klotho gene variations and parameters of mineral bone
metabolism for the development of LVH were des...igned. The five-year survival rate
was monitored.
Carriers of A-allele of the G-395A Klotho gene polymorphism, compared to non-Aallele
carriers, are significantly longer on chronic hemodialysis program (p=0.033),
started renal replacement therapy at an earlier stage of life (p=0.044), have
decreased concentration of Klotho protein (p=0.01), have increased concentration of
FGF23 (p=0.031) and phosphorus (p=0.016). The best prediction for the
development of LVH was reached by adding all three new parameters of mineral
bone metabolism and Klotho G-395A polymorphism; AUC has shown significant
improvement from 0.596 to 0.806 (p< 0.001), and an improvement in patient
reclassifications for 82.1% (95% CI 42.9–121.3%). During the five-year follow-up,
the mortality rate was 52.1%, where 46.6% had cardiovascular complications as a
direct cause of death.
The G-395A Klotho polymorphism is determined due to faster progression of
chronic kidney disease in A-allele carriers, decreased concentration of Klotho
protein, and increased concentration of FGF23 and phosphorus, which suggest that
they have a higher risk for the development of cardiovascular complications. This
research has shown the prediction power of the new parameters of mineral bone
metabolism for the development of LVH and mortality. Knowledge of Klotho gene
variations contributes to the personalised management of patients, which, alongside
the application of adequate therapeutic means and procedures, increases the quality
of life and more prolonged survival of the hemodialysis patients.