Cardiac and vessels remodeling as a result of FGF-23/ Klotho factors imbalance in chronic kidney disease patients

The aim of the study was to assess the correlation between the levels of FGF-23, Klotho, and serum troponin I (a classic biomarker of cardiac muscle damage) and clinical signs of cardiac and vascular remodeling. Material and methods. 130 patients with chronic kidney disease (CKD) stages 2-5D without cardiovascular disease (CVD) clinical manifestations were icluded in the study. In all participants were measured serum levels of FGF-23, Klotho and troponin I (sTr-I), also echocardiography and sphygmography were performed. Results. FGF-23 level correlated with sTr-I (r=0,512; p <0,01), presence of eccentric left ventricular hypertrophy (LVH; r=0,545; p <0,01), LV diastolic dysfunction (r=0,448; p <0,05), indicators of subendocardial blood flow (r=-0,469; p <0,05). At the same time, there was fixed no difference in the level of FGF-23 in patients with normal and high central (aortic) arterial pressure (CAP). Klotho's protein level correlated with concentric LVH (r=-0,463; p <0,01), LV diastolic dysfunction (r=-0,612; p <0,05), pulse wave velocity (PWV; r=-0,667; p <0,001 ), with indexes for estimation the cardiac structures calcification (ECSS; r =-0,581; p <0,01). Multivariate analysis revealed a positive independent association of FGF-23 with eccentric LVH (OR=1,056; 95% C1: 1,006-1,109; p=0,027). Protein Klotho acted as a negative determinant for concentric LVH (OR=0,988; 95% CI: 0,984-0,992; p=0,001), PWV (OR=0,984; 95% CI: 0,977-0,991; p <0,001) and ECSC (OR=0,991; 95% CI: 0,988-0,995; p <0,001). In addition, multivariate analysis showed a correlation between the Klotho protein level (OR=0,980; 95% CI: 0,964-0,996; p=0,016), FGF-23 (OR=3,145; 95% CI: 1,020-9,695; p=0,046) and sTr-I in blood serum. Conclusion. In patients with CKD stages 2-5D without clinical CVD manifestations, an increased serum FGF-23 level and a decreased level of serum Klotho protein are associated with a high risk of cardiovascular diseases development: FGF-23 level - with eccentric LVH (regardless of CAP), Klotho protein level - with concentric LVH, increased PWV and ECSC. Moderately elevated sTr-I level may be the first manifestation of FGF-23/Klotho protein factors imbalance in CKD.

FGF-23, chronic kidney disease, FGF-23, Klotho protein, troponin I, remodeling of the cardiovascular system