Povezanost varijacija u genu za Klotho protein, parametara mineralno-koštanog metabolizma i ehokardiografskih karakteristika kod bolesnika na hemodijalizi
Mineral bone metabolism disorder plays a major role in the etiopathogenesis ofcardiovascular events in hemodialysis patients. In recent years, many newparameters associated with the homeostasis of mineral bone metabolisms, such asfibroblast growth factor 23 (FGF23) and Klotho protein, have been discovered. Themain goal of this study is to discover interrelationships between Klotho protein genevariations, mineral bone metabolism, and left ventricular hypertrophy (LVH) inhemodialysis patients.The study included 142 patients who were genotyped for G-395A and C1818TKlotho gene polymorphism. Laboratory analyses were performed for routineparameters of mineral bone metabolism (calcium, phosphorus, parathyroidhormone, and alkaline phosphatase) and new parameters (FGF23, Klotho, andvitamin D) and echocardiographic examination. Models for the determination ofpredictive capabilities of Klotho gene variations and parameters of mineral bonemetabolism for the development of LVH were designed. The five-year survival ratewas monitored.Carriers of A-allele of the G-395A Klotho gene polymorphism, compared to non-Aallelecarriers, are significantly longer on chronic hemodialysis program (p=0.033),started renal replacement therapy at an earlier stage of life (p=0.044), havedecreased concentration of Klotho protein (p=0.01), have increased concentration ofFGF23 (p=0.031) and phosphorus (p=0.016). The best prediction for thedevelopment of LVH was reached by adding all three new parameters of mineralbone metabolism and Klotho G-395A polymorphism; AUC has shown significantimprovement from 0.596 to 0.806 (p< 0.001), and an improvement in patientreclassifications 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 adirect cause of death.The G-395A Klotho polymorphism is determined due to faster progression ofchronic kidney disease in A-allele carriers, decreased concentration of Klothoprotein, and increased concentration of FGF23 and phosphorus, which suggest thatthey have a higher risk for the development of cardiovascular complications. Thisresearch has shown the prediction power of the new parameters of mineral bonemetabolism for the development of LVH and mortality. Knowledge of Klotho genevariations contributes to the personalised management of patients, which, alongsidethe application of adequate therapeutic means and procedures, increases the qualityof life and more prolonged survival of the hemodialysis patients.
Biografija autora: list 151,Bibliografija: listovi 130-150. Datum odbrane: 23.11.2022. Internal medicine, biochemistry
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