Fibroblast Growth Factor 23 in Feline Chronic Kidney Disease

Abstract

Background: Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone involved in the pathogenesis of secondary renal hyperparathyroidism (SRHP) in humans. There are no published studies examining feline FGF-23.Objectives: Validation of a method for FGF-23 quantification in feline plasma and assessment of the associations among plasma FGF-23, PTH, creatinine, and phosphate concentrations in cats with chronic kidney disease (CKD).Animals: One hundred nonazotemic and azotemic geriatric (>9 years) client-owned cats. Methods: Retrospective cross-sectional study: Cats were categorized into 4 groups: control group (plasma creatinine (Cr) 2.0 mg/dL), stage 2 (Cr 2.1-2.8 mg/dL), stage 3 (Cr 2.9-5.0 mg/dL), stage 4 (Cr >5.0 mg/dL). Stages 2 and 3 were further subdivided based on International Renal Interest Society targets for plasma phosphate concentration (PO 4 ): stage 2a (PO 4 4.5 mg/dL), stage 2b (PO 4 >4.5 mg/dL), stage 3a (PO 4 5 mg/dL), stage 3b (PO 4 >5 mg/dL). Plasma FGF-23 concentrations were measured by a human intact FGF-23 ELISA. Descriptive statistics and linear regression were performed.Results: The ELISA demonstrated acceptable precision, reproducibility, and specificity. Plasma FGF-23 concentrations increased with increasing plasma creatinine concentrations and were significantly different between all groups (P < .008). Plasma FGF-23 concentrations were significantly higher in cats in stage 2b than stage 2a (P = .008) and in stage 3b than in stage 3a (P = .012). Phosphate, log creatinine, total calcium, log parathyroid hormone, and packed cell volume were all independent predictors of FGF-23.Conclusions and Clinical Importance: FGF-23 concentrations increase with increasing stage of feline CKD and might be a marker or mediator of feline SRHP.

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

“…The samples had been stored in 0.5 mL aliquots that had not undergone any freeze‐thaw cycles in the majority of cases. In a small number of cases aliquots used to measure FGF‐23 had undergone1 freeze‐thaw cycle, which has previously been shown not to significantly affect feline FGF‐23 concentrations 6. PTH concentrations were measured using a validated total intact PTH immunoradiometric assay,3 as previously described 20.…”

“…Samples with a PTH concentration below the lower limit of detection (<5.2 pg/mL)20 were assigned a value of 2.6 pg/mL. Intact plasma FGF‐23 concentrations were measured using a validated ELISA4 as previously described 6…”

Aging in the Canine Kidney

“…The kidneys of these mice had significantly more interstitial fibrosis, nephrocalcinosis, and dysmorphic tubules when compared with age matched controls. 39 FGF-23 is upregulated in chronic kidney disease in humans 18 and cats 25 but has not been examined in dogs. The role of the renin-angiotensin-aldosterone system in potentiating renal injury has been recognized.…”

Fibroblast Growth Factor 23

“…66 No matter the stage of kidney disease, and despite similar plasma creatinine concentrations, cats with hyperphosphatemia had higher plasma FGF23 concentrations than did normophosphatemic cats. 66 Serum FGF23 concentrations also exponentially increased as glomerular filtration rate decreased, and this partially paralleled increases in serum creatinine concentrations. 58 Feeding a protein-and phosphate-restricted diet to cats with chronic kidney disease resulted in a decrease in plasma FGF23 concentration (regardless of the plasma phosphate concentration) and a decrease in plasma phosphate concentration (in those cats that were hyperphosphatemic) but no decrease in plasma creatinine concentration.…”

“…40,58,66,67,209 FGF23 increases as the stage of kidney disease increases in cats. 66 No matter the stage of kidney disease, and despite similar plasma creatinine concentrations, cats with hyperphosphatemia had higher plasma FGF23 concentrations than did normophosphatemic cats. 66 Serum FGF23 concentrations also exponentially increased as glomerular filtration rate decreased, and this partially paralleled increases in serum creatinine concentrations.…”