Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Physiology

Background, left ventricular hypertrophy (LVH) is one of the major cardiovascular complication of Chronic kidney disease (CKD). Activation of fibroblast growth factor receptor (FGFR4 and 1) may contribute to the complex pathogenesis of LVH. The aim of this work was to evaluate the therapeutic and prophylactic role of the small molecule inhibitor of FGFR4 (BLU9931) and the small molecule inhibitor of FGFR1 (AZD4547) in alleviating uremic cardiomyopathy. Methods, CKD was induced in rats by 5/6 subtotal nephrectomy operation. fifty Adult male Wistar rats were randomly divided into five groups as follows: (1) Control group, (2) Sham {u2013}operated group, (3) 5/6 subtotal nephrectomy group, (4) 5/6 subtotal nephrectomy + FGFR4 inhibitor: BLU9931 {RF B1}, (5) 5/6 subtotal nephrectomy + FGFR1 inhibitor: AZD4547{] RF B2}. Arterial Blood pressure, electrocardiography ECG and echocardiography ECHO measurement and serum urea and creatinine were recorded in all groups. Results, administration of both the small molecule FGFR4 inhibitor BLU9931 and the small molecule FGFR1 inhibitor AZD4547 2 weeks after the operation resulted in amelioration of cardiac hypertrophy in both RF B1 and RF B2 group at the fifth week. By analysis of echocardiography data, a significant decline in IVSd and LVPWd thicknesses were observed in both RF B1 and RF B2 groups back to the control value. On the other hand, there was no changes in EF% and FS% throughout the study in RF B1 and RF B2. Also, we report significant decrease in the serum urea and serum creatinine in both treated groups. Conclusion, the results of the present study suggested that administration of the small molecule inhibitor of FGFR4: BLU9931 and the small molecule AZD4547 inhibitor of FGFR1 Combined with proper control of renal hypertension can be an early effective prophylactic treatment for preventing adverse uremic cardiovascular complications

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