Interplay Between Fibroblast Growth Factor-19, Beta-Klotho and Receptors Impact Cardiovascular Risk in Chronic Kidney Disease

Chronic kidney disease (CKD) markedly increases the risk of cardiovascular events (CVE), yet conventional biomarkers often fail to capture this excess risk. We evaluated whether circulating levels and genetic variability within the FGF19/β-Klotho/FGFR axis contribute to CV risk stratification in CKD. In 579 CKD patients, plasma FGF19 and β-Klotho con-centrations were quantified, and 64 genetic variants across FGF19, KLB, FGFR1 and FGFR4 genes were analyzed. Cluster analysis identified three distinct biomarker profiles, with one cluster—characterized by low/intermediate FGF19 and markedly elevated β-Klotho—showing significantly reduced CV event-free survival. After adjustment for clinical covariates, this cluster was independently associated with higher CV risk [HR=2.97 (1.12–7.92), p=0.029]. Two genetic variants also showed independent associa-tions: FGFR1 rs2288696 (protective) [HR=0.51 (0.27–0.95), p=0.029] and KLB rs2687971 (risk-increasing) [HR=2.03 (0.97–4.27), p=0.046]. A combined CV risk model incorporating biomarker clusters, relevant SNPs and traditional risk factors achieved good discrimina-tive ability (C-index = 0.80), with the FGF19/β-Klotho cluster showing predictive im-portance comparable to diabetes and previous CV history. These findings suggest that in-tegrating FGF19-Klotho biomarkers with genetic information may enhance CV risk pre-diction in CKD.