Serum fibroblast growth factor 23 (FGF-23): associations with hyperphosphatemia and clinical staging of feline chronic kidney disease

Abstract

Fibroblast growth factor 23 (FGF-23) is an independent monitor of the progression of chronic kidney disease (CKD) in human medicine, and FGF-23 may have value as a biomarker in feline CKD. We evaluated the relationship between serum FGF-23 and CKD stages, and the effect of age on FGF-23 in normal cats. We measured FGF-23 and intact parathyroid hormone (iPTH) concentrations by ELISA, with intra- and inter-assay CVs ≤ 15%. The percentage recovery of FGF-23 and iPTH remained stable for up to 7 d in samples stored at −20°C and −80°C. We measured FGF-23 in 304 cats, among which 196 were diagnosed with CKD. The 108 clinically healthy cats were divided into 5 subgroups based on growth stage (0–2 y, 3–6 y, 7–10 y, 11–14 y, ≥ 15 y). No statistical difference was found in FGF-23 among age groups ( p = 0.15) or by sex in healthy subjects. Using the International Renal Interest Society guideline, 34 cats were defined as CKD stage 1, 74 stage 2, 51 stage 3, and 37 stage 4. FGF-23 was higher in cats in all CKD stages than in controls. Higher serum phosphorus was observed in stage 3 ( p = 0.04) and 4 ( p < 0.01) compared to controls. iPTH increased as CKD progressed. Pearson analysis indicated a positive linear relationship between FGF-23 and iPTH (control: r = 0.70, p < 0.01; CKD: r = 0.46, p = 0.02). FGF-23 may be a useful biomarker of feline CKD and may precede hyperphosphatemia in advanced feline CKD.

Relationship between FGF 23, SDMA, Urea, Creatinine and Phosphate in Relation to Feline Chronic Kidney Disease

“…Because previously published studies [ 22 , 23 , 24 , 25 , 26 ] came with the hypothesis that FGF 23 should increase with increasing SDMA and should be positively correlated to phosphate concentrations, we also evaluated these two parameters. Studies indicate that FGF 23 increases with the progression of CKD in humans, dogs and cats [ 22 , 23 , 24 , 25 ], and therefore could be a biomarker for the early detection of CKD [ 27 ].…”

Serum fibroblast growth factor-23 concentrations in young and mature adult cats with chronic kidney disease

“…8 A recent study investigated the association between a cat’s life stages and serum FGF-23 concentrations and showed that there was no effect of age on FGF-23 in healthy cats. 28 The difference in FGF-23 levels of healthy cats between the studies can be caused by variation of FGF-23 assay rather than age. Thus, the reference interval of feline FGF-23 should be determined per FGF-23 assay.…”

Fibroblast growth factor and kidney disease: Updates for emerging novel therapeutics

“…The advancement of FGF/FGFR targeting therapies is the basis of several preclinical, clinical, and basic investigations. Various nonselective FGF/FGFR inhibitors have been endorsed for cancer or other disease treatment (Degirolamo et al, 2016;Ghedini et al, 2018;Hallinan et al, 2016;Hierro et al, 2015;Lin et al, 2021;Memmos & Papagianni, 2021;Porta et al, 2017;Ronca et al, 2015;Xue et al, 2018), but data highlights a variety of obstacles affecting their use in the clinical practice. It seems required to identify FGF/FGFR alterations and some modifications that may foresee and monitor the response of treatment, to determine the contribution of the FGF/FGFR system in the onset of mechanisms of drug resistance, and to develop effective combinations of FGF/FGFR inhibitors with additional targeted rehabilitations.…”