FGF23 and Risk of Heart Failure
Heart failure (HF) is a leading cause of death in individuals with chronic kidney disease (CKD). CKD is also known as a “silent killer” as many people live with the disease without developing symptoms. CKD is a progressive disease and it is estimated that around 10% of the adult general population worldwide is affected (1). A large number of individuals are undiagnosed as demonstrated in a study from the UK in 3200 participants aged over 60 years (2).
FGF23 and Risk of Heart Failure
What is CKD?
Chronic kidney disease is a condition where kidney function gradually declines. The kidneys play a crucial role in filtering waste from the blood with the help of nephrons. A constant increase in damaged and non-functioning nephrons lead to the progression of the disease.
How does CKD cause Heart Failure?
Impaired kidney function places an additional strain on the heart, as it needs to pump harder to get blood to the kidneys. Changes in blood pressure is also a complication in CKD that can ultimately lead to heart disease. One suggested mechanism for the development of HF in CKD patients is linked to highly elevated levels of FGF23 (3).
What is the role of FGF23 in Heart Failure?
Fibroblast growth factor 23 (FGF 23) is a bone-derived hormone that regulates phosphate and vitamin D. In individuals with CKD, circulating FGF23 blood levels gradually increase with declining kidney function. In patients with end-stage renal disease, FGF23 levels are highly elevated up to 1000-fold above the normal range (4).
Numerous studies indicate that high FGF23 concentrations have a direct effect on the heart and the cardiovascular system. Elevated FGF23 levels have been linked to an increased risk of cardiovascular events, including heart failure, cardiovascular mortality, and left ventricular hypertrophy (5, 6). The precise mechanisms by which FGF23 impacts the heart are still being explored. One potential pathway could be linked to the discovery of FGF23 receptors expressed in the heart by cardiomyocytes. Specific binding of FGF23 to these receptors may directly induce hypertrophy. Additional pathways are under investigation.
In a recent large multicenter prospective cohort study in over 3500 participants, researchers investigated the relationship between elevated FGF23 levels and the risk of HF in individuals with varies HF subtypes. The authors concluded that elevated FGF23 levels were associated with increased risks for all HF subtypes highlighting the need for further research on FGF23 as a potential target in HF prevention in individuals with chronic kidney disease (3).
What are the methods for measuring FGF23?
Circulating blood FGF23 levels can be measured with immunoassays. A commonly employed technique is the ELISA assay (enzyme linked immunosorbent assay).
FGF23 ELISA assays employ specific antibodies designed to detect FGF23 present in the sample (serum / plasma). Currently, two commercially available assays are used for the measurement of circulating FGF23 in blood samples (7):
- ELISA for measuring Intact FGF23
The full length, biologically active form of the hormone is intact FGF23 (iFGF23), consisting of the complete and full-length FGF23 protein structure without enzymatical cleavage. The ELISA utilizes two antibodies that target the N-terminal part and the C-terminal domain of the FGF23 molecule, respectively.
- ELISA for measuring FGF23 C-terminal
C-terminal fragments of FGF23 (cFGF23) result from the enzymatic cleavage of the intact FGF23 molecule. The ELISA utilizes two antibodies that bind to epitopes that are located in the c-terminal domain of the FGF23 molecule.
OF NOTE: all FGF23 c-terminal assays that are commercially available detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule (7).
BIOMEDICA offers two ELISA kits that reliably quantify FGF23 concentrations in human serum and plasma samples:
FGF23 – complete ready to use ELISA kits – User-Friendly and Reliable
- FGF23 intact ELISA (cat. no. BI-20700)
- FGF23 (C-terminal) ELISA (cat. no. BI-20702)
BIOMEDICA FGF23 intact ELISA assay (#BI-20700)
BIOMEDICA FGF23 multimatrix (C-terminal) ELISA assay (#BI-20702)
- Validated FGF23 ELISA kits according to international quality guidelines
- Numerous citations /references in top-ranking journals
FGF23 ELISA assays are Developed & Manufactured by Biomedica
Literature
- Epidemiology of chronic kidney disease: an update 2022. Kovesdy CP. Kidney Int Suppl (2011). 2022. 12(1):7-11. PMID: 35529086; PMCID: PMC9073222
- Prevalence of chronic kidney disease in the community using data from OxRen: a UK population-based cohort study. Hirst JAet al., Br J Gen Pract. 2020. 26;70(693):e285-e293. PMID: 32041766; PMCID: PMC7015167.
- Chronic Renal Insufficiency Cohort (CRIC) study investigators. Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study. Leidner Aset al.,Kidney Med. 2023. 5(11):100723. PMID: 37915961; PMCID: PMC10616385.
- Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. Gutierrez O et al., Journal of the American Society of Nephrology. 2005;16(7):2205–2215.
- FGF23 and Cardiovascular Risk. Prié D. Ann Endocrinol (Paris). 2021. 82(3-4):141-143. PMID: 32950228.
- Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne). Leifheit-Nestler M, Haffner D 2018. 28;9:278. PMID: 29892269; PMCID: PMC5985311.
- The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Calcif Tissue Int. Heijboer AC, Cavalier E. 2023 Feb;112(2):258-270. PMID: 35665817; PMCID: PMC9859838.