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

Abstract

BackgroundFibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat.ObjectivesTo investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months.Animals214 azotemic, client‐owned cats (≥9 years).Methods Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression.ResultsIn the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression.Conclusions and Clinical ImportancePlasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD.

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease

“…Of the 421 eligible cats, 88 cats had no residual plasma sample available for measurement of tMg, 157 cats lacked baseline information on plasma FGF23 concentration, and 2 samples were grossly hemolyzed. Thus, 174 cats were enrolled in our study, some of which had been included in previous studies . No significant differences were observed between baseline characteristics of the 174 included cats and of the 247 eligible cats that were excluded from analysis because of lack of a residual plasma sample or plasma FGF23 measurement (data not shown).…”

“…Cats were categorized into 2 groups: a progressive CKD group that showed >25% increase in plasma creatinine concentration within the first 12 months of diagnosis, and a stable CKD group that did not show an increase >25% in plasma creatinine concentration. The cut‐point of 25% was based on the presumption that smaller changes could be caused by poor measurement precision rather than actual progression of azotemia . Only stable cats with follow‐up of ≥12 months were included in our analysis.…”

“…Interestingly, magnesium might be involved in FGF23 regulation, because an inverse association between these two variables was observed in human CKD patients on hemodialysis, and serum FGF23 concentrations were increased in rodents fed a magnesium deficient diet . Plasma FGF23 itself is a strong predictor of survival and progression in cats with CKD …”

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

“…1 More recently epidemiological studies have focused on the role of other molecules involved in phosphorus homeostasis with both PTH and FGF23 being associated with the development and survival of cats with CKD. [115][116][117] Perhaps the most convincing evidence that there is likely to be a role for phosphorus homeostasis in the progression of CKD comes from the studies that have demonstrated improved survival in those cats that are fed a phosphate restricted diet with evidence of modulation of these important regulatory hormones. 114,190,191 …”

“…40 Epidemiological studies have evaluated factors associated with the development of azotemia, survival of cats with CKD and also demonstrating a more progressive phenotype of CKD. 24,[38][39][40][115][116][117] From the experimental and human literature there are a number of key pathophysiological mechanisms which have been implicated in both the development and progression of CKD. An understanding of these mechanisms is important not only because many may be applicable and translated to feline CKD but also because they provide potential targets for therapy in order to slow disease progression.…”