FGF-23 and Its Newly Identified Prognostic Role in Cats With CKD
Veterinarians specializing in feline patients dedicate considerable time to diagnosing, treating, and managing chronic kidney disease (CKD). We constantly seek new diagnostic and therapeutic advancements that facilitate earlier identification and intervention. Fibroblast growth factor 23 (FGF-23) is a biomarker that can help detect early CKD in cats that may benefit from dietary changes to slow disease progression. A recent study in The Veterinary Journal assessed how varying levels of FGF-23 in cats with CKD influence their prognosis. Here we'll examine some of the study's findings, focusing specifically on the role this biomarker plays in the prognosis of CKD among feline patients.
What Is FGF-23?
Fibroblast growth factor 23 is a biomarker produced by osteoblasts and osteocytes. Its primary function is to regulate the phosphate entering the extracellular fluid from bones and through the gastrointestinal tract, with its excretion handled by the kidneys. Throughout this process, it interacts with other renal hormones such as calcitriol and parathyroid hormone (PTH). FGF-23 inhibits the activation of calcitriol and the secretion of PTH, thereby influencing the body's balance of calcium and phosphate. After extensive research, the academic consensus suggests that FGF-23 has evolved as a crucial component in a system that enables terrestrial animals (like our feline patients) to maintain healthy bone turnover without losing calcium and phosphate to other tissues.1
FGF-23 and CKD
An imbalance, such as an elevation of serum FGF-23 in our feline CKD patients, is the earliest indicator of a mineral bone disorder (MBD).2 Even when serum phosphorus levels on blood chemistry panels remain within the reference range, serum FGF-23 levels increase at this stage, biochemically indicating a reduced glomerular filtration rate and limited phosphate excretion. The initial normalization of serum phosphorus is only possible because adaptive responses in the diseased kidneys help excrete the same amount of phosphate consumed daily. However, as kidney disease progresses, these adaptive responses become ineffective, leading to the accumulation of phosphate and calcium ions in the blood and extracellular fluids. Eventually, these ions are deposited in soft tissues, depleting the bone's reserves of calcium and phosphate.
Research has also shown that plasma concentrations of FGF-23 rise in line with the IRIS stage of CKD in feline patients. One study found that FGF-23 levels significantly increased in azotemic cats compared to non-azotemic cats.3 A second study observed that FGF-23 levels decreased when dietary phosphate restrictions were implemented for cats when blood phosphate levels were within the targeted IRIS range.4 These findings suggest that FGF-23 may serve as a predictive biomarker for the development of azotemia and as a marker to monitor the response to dietary phosphate restriction in CKD cats. Most importantly, it should be emphasized that serum FGF-23 elevation occurs before hyperphosphatemia in cats.
Finally, a pivotal study examined cats diagnosed with chronic kidney disease at the same IRIS stage of 2 or 3, grouping them based on their plasma phosphate concentrations. In this study, hyperphosphatemic patients exhibited significantly higher FGF-23 levels than those with normal blood phosphate concentrations.5 Similar to human patients, elevated FGF-23 concentrations correlated with faster disease progression and shorter survival times in cats with chronic kidney disease. Higher serum FGF-23 levels at the time of CKD diagnosis indicate a poor prognosis and can serve as predictors in client communications.
How To Use FGF-23 and Other Methods for Monitoring CKD Patients
As we continue to uncover earlier biomarkers for diagnosing, treating, and managing CKD, effective communication with clients regarding care expectations and disease progression remains essential. Wellness screening is strongly recommended as part of a veterinary practice's mission. Some practices categorize testing based on patient demographics, creating specific lab tests by breed, age, or other factors.
For feline patients diagnosed with chronic kidney disease, we must guide cat caregivers on what routine monitoring entails (CBC, chemistry/electrolyte panels, urinalysis, blood pressure, etc.), and how specific tests like FGF-23 can inform prognosis. FGF-23 aids in identifying cats with early chronic kidney disease who could benefit from dietary phosphate restrictions. It also provides valuable insights into disease progression and survival times.
References:
- K. Kato, et al. Polypeptide Ga1NAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 require O-glycosylation. Journal of Biological Chemistry, 281 (27) (2006), pp 18370-18377.
- J. Alexander, et al. Effects of the long-term feeding of diets enriched with inorganic phosphorus on the adult feline kidney and phosphorus metabolism. British Journal of Nutrition, 121(3) (2019), pp. 249-269.
- Finch NC, Geddes RF, Syme HM, Elliott J. Fibroblast growth factor 23 (FGF-23) concentrations in cats with early nonazotemic chronic kidney disease (CKD) and in healthy geriatric cats. J Vet Intern Med. 2013;27(2):227–233. doi:10.1111/jvim.12036
- Geddes RF, Elliott J, Syme HM. The effect of feeding a renal diet on plasma fibroblast growth factor 23 concentrations in cats with stable azotemic chronic kidney disease. J Vet Intern Med. 2013;27(6):1354–1361. doi:10.1111/jvim.12187
- Geddes RF, Finch NC, Elliott J, Syme HM. Fibroblast growth factor 23 in feline chronic kidney disease. J Vet Intern Med. 2013;27(2):234–241. doi:10.1111/jvim.12044
