FGF-23 in Feline CKD: An Early Signal of Phosphate Dysregulation

A cat with early chronic kidney disease (CKD) may have a normal serum phosphate concentration. Does that mean phosphate balance is still normal? 

Not necessarily. Fibroblast growth factor-23 (FGF-23) may reveal phosphate dysregulation before conventional changes in serum phosphate or parathyroid hormone (PTH) become apparent. This makes it a potentially useful biomarker when assessing cats in the earlier stages of CKD. 

Why Look Beyond Serum Phosphate? 

As kidney disease progresses, reduced phosphate excretion can disrupt calcium-phosphate homeostasis. This contributes to chronic kidney disease-mineral and bone disorder (CKD-MBD), characterized by increasing serum phosphate concentrations, increased PTH secretion, and osteodystrophy^[1]. 

FGF-23 is one of the hormones involved in maintaining phosphorus and calcitriol balance. Produced by osteocytes and osteoblasts, it promotes urinary phosphorus excretion by inhibiting proximal tubular sodium-phosphorus cotransporters. It also reduces intestinal phosphorus reabsorption by impairing renal calcitriol production^[1]. 

The clinically interesting point is timing. 

In cats, FGF-23 may increase before serum phosphate becomes abnormal. That potentially provides an earlier indication that phosphate regulation is being affected by declining renal function. 

An Increase Can Precede Hyperphosphatemia 

Plasma FGF-23 (pFGF-23) concentrations have been found to be higher in cats with CKD and hyperphosphatemia than in cats with normophosphatemia within the same IRIS stage^[2]. However, pFGF-23 is not consistently correlated with phosphate concentration in cats with normal renal function^[3],[4]. 

This suggests that interpretation should not simply be based on phosphate concentration alone. 

Several other factors, including total calcium, magnesium, PTH, and PCV, have also been associated with pFGF-23 concentrations in cats with CKD^[1]. 

More importantly, increased FGF-23 has been detected in situations where conventional phosphate measurements may still appear reassuring. 

Non-azotemic geriatric cats that subsequently developed azotemia within 12 months had significantly higher baseline pFGF-23 concentrations than cats whose renal function remained stable, despite similar phosphate, PTH, and sCr concentrations at baseline. Similarly, pFGF-23 was increased in non-azotemic cats with SDMA concentrations >14 μg/dL even without hyperphosphatemia^[3],[4]. 

These findings raise an important clinical possibility: Phosphate dysregulation may already be developing before azotemia and hyperphosphatemia become evident. 

Can FGF-23 Help Guide Management?^[5] 

There is also evidence that pFGF-23 responds to dietary management. 

Feeding a renal diet decreased pFGF-23 concentrations in both hyperphosphatemic and normophosphatemic CKD cats. In hyperphosphatemic cats, this reduction occurred alongside significant changes in plasma phosphate and PTH concentrations. 

This suggests that a serial FGF-23 assessment could potentially provide additional information about changes in phosphate metabolism during CKD management. 

However, the evidence does not support treating an individual FGF-23 result as a standalone decision point. 

An Important Limitation: Individual Interpretation^[1] 

Cats with azotemic CKD generally have higher pFGF-23 concentrations than healthy cats, and concentrations increase with CKD severity. Higher baseline pFGF-23 has also been associated with CKD progression, defined as a >25% increase in sCr within 12 months of CKD diagnosis. 

But there is considerable overlap between the groups. Therefore, population-level differences cannot automatically be applied to an individual cat. 

Clinical Bottom Line 

FGF-23 offers a different perspective from traditional renal biomarkers. Rather than simply reflecting reduced GFR, it may provide an earlier indication of phosphate dysregulation associated with CKD. 

For the practicing veterinarian, its potential value lies in adding information to the broader clinical picture, particularly in geriatric or early CKD cats where serum phosphate, PTH, and sCr may not yet show substantial abnormalities. Further validation is still needed before pFGF-23 can be routinely relied upon for individual clinical decision-making.

References:

1. Kongtasai T, Paepe D, Meyer E, Mortier F, Marynissen S, Stammeleer L, Defauw P, Daminet S. Renal biomarkers in cats: A review of the current status in chronic kidney disease. Journal of veterinary internal medicine. 2022 Mar;36(2):379-96. https://academic.oup.com/jvim/article-pdf/36/2/379/66666729/jvim16377.pdf
2. Geddes RF, Finch NC, Elliott J, Syme HM. Fibroblast growth factor 23 in feline chronic kidney disease. Journal of veterinary internal medicine. 2013 Mar;27(2):234-41. https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.12044
3. 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. Journal of Veterinary Internal Medicine. 2013 Mar;27(2):227-33. https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.12036
4. Sargent HJ, Jepson RE, Chang YM, Biourge VC, Bijsmans ES, Elliott J. Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats. Journal of veterinary internal medicine. 2019 Nov;33(6):2657-64. https://academic.oup.com/jvim/article-pdf/33/6/2657/66656463/jvim15590.pdf
5. 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. Journal of veterinary internal medicine. 2013 Nov;27(6):1354-61. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvim.12187