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


DOI: https://dx.doi.org/10.18565/therapy.2021.6.7-17

Milovanova L.Yu., Taranova M.V., Milovanova S.Yu., Kozlov V.V., Beketov V.D., Volkov A.V., Pasechnik A.I., Moiseev S.V.

1) I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University); 2) M.V. Lomonosov Moscow State University
Abstract. 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% CI: 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.
Keywords: remodeling of the cardiovascular system, Klotho protein, troponin I, FGF-23, chronic kidney disease
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About the Autors

Lyudmila Yu. Milovanova, MD, professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. Tel.: +7 (916) 164-14-00. E-mail: Ludm.milovanova@gmail.com. ORCID: 0000-0002-5599-0350
Marina V. Taranova, PhD, associate professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. E-mail: mvtaranova@mail.ru. ORCID: 0000-0002-7363-6195
Svetlana Yu. Milovanova, MD, professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. E-mail: sveta@milovanova.ru. ORCID: 0000-0002-2687-6161
Vasily V. Kozlov, PhD, associate professor of the Department of public health and health organization named after N.A. Semashko, Federal State Autonomous Educational Institution of I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119992, Moscow, 2/2 Bolshaya Pirogovskaya Str. E-mail: kvv.doc@gmail.com. ORCID: 0000-0002-2389-3820
Vladimir D. Beketov, PhD, associate professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. E-mail: beketov-vladimir@inbox.ru. ORCID: 0000-0002-6377-0630
Aleksey V. Volkov, PhD, associate professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. E-mail: a-1973@yandex.ru. ORCID: 0000-0002-1873-0189
Anastasia I. Pasechnik, resident of the Department of internal diseases, faculty of fundamental medicine, M.V. Lomonosov Moscow State University. Address: 119991, Moscow, 27/1 Lomonosovsky Avenue. E-mail: apgull@gmail.com. ORCID: 0000-0002-7544-3696
Sergey V. Moiseev, MD, professor, head of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119435, Moscow, 11/5 Rossolimo Str. E-mail: avt420034@gmail.com. ORCID: 0000-0002-7232-4640


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