Povezanost varijacija u genu za Klotho protein, parametara mineralno-koštanog metabolizma i ehokardiografskih karakteristika kod bolesnika na hemodijalizi

Abstract

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 designed. 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.