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Interplay Between Fibroblast Growth Factor-19, Beta-Klotho, and Receptors Impacts Cardiovascular Risk in Chronic
Laura González-Rodríguez1,2, Manuel Martí-Antonio3, Virginia Díaz-Acevedo1
1Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, 06006 Badajoz, Spain.
Journal of Clinical Medicine
|February 13, 2026
Summary
Biomarkers in the FGF19/β-Klotho/FGFR axis and genetic variants can improve cardiovascular risk prediction in chronic kidney disease (CKD) patients. Integrating these factors enhances risk stratification beyond traditional methods.
Area of Science:
- Endocrinology
- Nephrology
- Cardiology
Background:
- Chronic kidney disease (CKD) significantly elevates cardiovascular event (CVE) risk.
- Conventional biomarkers often underestimate this increased cardiovascular risk in CKD patients.
Purpose of the Study:
- To investigate the role of circulating FGF19/β-Klotho/FGFR axis levels and genetic variations in cardiovascular risk stratification among CKD patients.
- To assess if these factors improve prediction of cardiovascular events in this population.
Main Methods:
- Quantified plasma FGF19 and β-Klotho concentrations in 579 CKD patients.
- Analyzed 64 genetic variants across FGF19, KLB, FGFR1, and FGFR4 genes.
- Utilized cluster analysis to identify biomarker profiles and assessed their association with cardiovascular event-free survival.
Main Results:
- Identified three distinct biomarker profiles; one with low/intermediate FGF19 and high β-Klotho showed significantly reduced CV event-free survival.
- This specific biomarker cluster was independently associated with higher CV risk (HR = 2.97).
- Specific genetic variants (FGFR1 rs2288696, KLB rs2687971) and a combined risk model (C-index = 0.80) demonstrated predictive value.
Conclusions:
- Circulating FGF19-Klotho biomarkers and genetic information can enhance cardiovascular risk prediction in CKD.
- The FGF19/β-Klotho biomarker cluster offers predictive importance comparable to established risk factors.
- Integrating these novel markers may lead to improved clinical management and targeted interventions for high-risk CKD patients.
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