August 11, 2017

Fibroblast Growth Factor 23 Concentration in Canine CKD

Fibroblast growth factor 23, a protein that regulates phosphate homeostasis, increases in canine chronic kidney disease and is associated with serum phosphorus.
By JoAnna Pendergrass, DVM
A study recently published in Research in Veterinary Science reported that fibroblast growth factor 23 (FGF23), a protein that regulates phosphate homeostasis, increases in dogs with chronic kidney disease (CKD) and is associated with serum phosphorus. Study results, noted the authors, point toward a potential new treatment approach for managing canine CKD.

CKD, which is common in older dogs, is an irreversible disease characterized by a progressive loss of functional renal tissue; this tissue loss can lead to significant morbidity and mortality.

The disease is typically classified into 4 stages—International Renal Interest Society (IRIS) stages—according to azotemia severity. This classification is useful for guiding CKD treatment and monitoring.

During CKD, the glomerular filtration rate (GFR) decreases, causing plasma phosphorus concentrations to increase. FGF23 is part of a protein group called phosphatonins that regulate plasma phosphorus concentrations. FGF23 has a phosphaturic effect, enhancing renal elimination of phosphate. Previous studies have reported that FGF23 concentrations increase with CKD stage in dogs and cats to counteract increased phosphorus retention.

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Study Details
The authors collected serum samples from 14 dogs with CKD and 20 non-azotemic dogs. The following analytes were measured:
  • Urea
  • FGF23
  • Calcium
  • Creatinine
  • Phosphorus
  • Parathyroid hormone (PTH)
Demographic information on the dogs’ age, breed, and sex was also collected. Dogs with CKD had a median age of 13.5 years, making them markedly older than non-azotemic dogs, whose median age was 8 years.

Concentrations of all analytes except calcium were significantly higher in dogs with CKD than in non-azotemic dogs; in particular, the median FGF23 concentration was approximately 5,200 pg/mL in dogs with CKD and 259 pg/mL in non-azotemic dogs. Importantly, the significant increases in serum phosphorus and PTH in dogs with CKD suggest that the increased FGF23 was unable to fully compensate for the dogs’ decreasing GFR.

For dogs with CKD, no significant differences in analyte concentrations were detected between IRIS stages 2, 3, and 4, likely because of the small number of dogs represented at each stage. However, compared with non-azotemic dogs, dogs with CKD had significantly higher analyte concentrations at these IRIS stages.

Regression analysis demonstrated significant associations of age and serum FGF23 concentration with IRIS stage, suggesting that these 2 factors are significant predictors of IRIS stage. This analysis also indicated that serum concentrations of phosphorus and FGF23 were significantly associated with each other—a finding that has also been observed in humans and cats with CKD.

Looking Forward
The authors suggested evaluating whether a phosphate-restricted diet would decrease plasma phosphorus and FGF23 concentrations in dogs with CKD, as has been shown in cats with CKD. In addition, they noted that a treatment approach targeting the phosphatonin pathway could provide a feasible option for controlling plasma phosphorus levels in CKD.

 
Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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