Serum troponin-I as a marker of fibroblast growth factor-23 (FGF-23) cardiotoxic effect, in patients with chronic kidney disease

Aim. It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD). Materials and methods. The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP >160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)). Results and discussion. The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p<0.01), LVMI (r=0.528; p<0.05), eccentric type of myocardial remodeling (MR; r=0.509; p<0.01), left ventricular diastolic dysfunction (DD; r=0.458; p<0.05), BSE (r=-0.499; p<0.05), PWV (r=0.514; p<0.01). Importantly, mean serum FGF-23 levels were not statistically significantly different in patients with elevated levels of CBP (CBP >120/80 mm Hg), and in patients with normal levels of CBP (CBP=90-120 / 60-79 mm Hg; p=0.071). At the same time, the serum level of Tr-I correlated with LVMI (r=0.567; p<0.05), eccentric type MR (r=0.461; p<0.01), DD (r=0.473; p<0.05), duration of CKD (r=0.512; p<0.05), BSE (r=-0.497; p<0.01), CBP (r=0.534; p<0.01). We revealed negative correlations between serum levels of Klotho and followed parameters: Tr-I (r=-0.537; p<0.01), PWV (r=-0.647; p<0.01), CCS (r=-0.612; p<0.01), LVMI (r=-0.539; p<0.01), concentric type MR (r=-0.528; p<0.01). According to multivariate analysis (logistic regression), a significant association there was only between elevated FGF-23 and elevated Tr-I in CKD patients without CVD. Conclusion. Detectable Tr-I serum levels without clinical signs of CVD and severe AH in patients with CKD is associated mainly with elevated serum levels of FGF-23.

FGF-23, Klotho, chronic kidney disease, FGF-23, Klotho, troponin I (Tr I)