Cardiovascular remodeling as a result of fibroblast growth factor-23 (FGF-23)/Klotho imbalance in patients with CKD

Abstract

Background: In chronic kidney disease (CKD) cardiovascular remodeling (CVR) is very frequent compared with general population and, as suppose, may be associated with «new» renal risk factors. The aim of study was to estimate association of new serum biomarkers (FGF-23, Klotho) and traditional biomarker of cardiac damage-serum Troponin I (sTr-I) with signs of CVR.

Methods: One hundred thirty CKD G1-5D patients without cardiovascular disease (CVD) clinical manifestation were included. We measured serum FGF-23, Klotho and sTr-I. The instrumental methods were: echocardiography, SphygmoCor test [Pulse Wave Velocity (PWV), Central (aortic) Blood Pressure (CBP), Subendocardial Blood Supply (SBS)].

Results: FGF-23 level correlated with: sTr-I (r = 0.512; p < 0.01), eccentric left ventricular hypertrophy, LVH (r = 0.543; p < 0.01), SBS (r = - 0.499; p < 0.05). There were no differences of FGF-23 level in patients with normal and high CBP. Klotho correlated with concentric LVH (r = - 0.451; p < 0.01), PWV (r = - 0.667; p < 0.001), Cardiac Calcification Score, CCS (r = - 0.581; p < 0.01). Multivariate analysis revealed positive independent association of FGF-23 with eccentric LVH (OR = 1.036, 95% CI (1.004-1.068); p = 0.038). Klotho was a negative determinant for concentric LVH (OR = 0.990, 95% CI 0.987-0.994; p < 0.001), increased PWV (OR = 0.984, 95% CI (0.977-0.991); p < 0.001) and CCS (OR = 0.991, 95% CI (0.988-0.995); p < 0.001). In addition, multivariate analysis revealed a relationship between serum Klotho (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 troponin I level.

Conclusion: In CKD patients without CVD clinical manifestation increased serum FGF-23 level and decreased Klotho are associated with CVR: FGF-23 with eccentric LVH (independently of CBP), Klotho determinate concentric LVH, PWV and CCS. Moderately elevated sTr-I levels may be a manifestation of FGF-23/Klotho imbalance in CKD.

Keywords: Cardiovascular remodeling; Chronic kidney disease (CKD); FGF-23; Klotho; Troponin I.