The diagnosis of chronic kidney disease (CKD) in cats is currently made using creatinine as an indirect marker of glomerular filtration rate (GFR), together with historical and clinical information and evaluation of urine concentrating ability. However, creatinine is recognised to be insensitive for the early decline in GFR. Symmetric dimethylarginine (SDMA) is a novel biomarker of GFR, with studies suggesting it may be more sensitive than creatinine in detecting this early decline. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone known to increase with declining GFR and has been shown to be predictive of the onset of azotemia in cats >9 years, indicating disturbed phosphate homeostasis.

The introduction of SDMA, has led to the identification of cats where SDMA is increased but plasma creatinine remains within reference interval (RI). There is currently little understanding of the metabolic changes present in these cats. The aim of this study was to examine the relationship between plasma FGF-23 and SDMA concentrations in non-azotemic geriatric cats.

Clinicopathological information from cats (≥8 years) was sourced from the records of two first opinion practices. Cats with a current or historical diagnosis of azotemic CKD (creatinine >177 µmol/L), a serum thyroxine >40 nmol/L or other chronic disease were excluded. Cats were categorised into two groups: elevated SDMA (>14 µg/dl) and SDMA within RI (≤14 µg/dl). Stored samples were used to quantify FGF-23 in all cats. Data are presented as median [25th, 75th percentile]. Comparisons were made between groups using Mann-Whitney U tests and relationships between numerical variables were evaluated using Spearman's correlation.

Twenty-eight cats with elevated SDMA (17 [16, 19] µg/dl) and 61 cats with SDMA within reference interval (11 [10, 12] µg/dl) were included. Cats with elevated SDMA had significantly higher FGF-23 (377.7 [202.6, 610.9] pg/ml vs. 219.6 [143.2, 295.1] pg/ml, p= 0.003) and creatinine (156 [141.8, 171.5] µmol/L vs. 128 [109, 148] µmol/L, p< 0.001) concentrations. Phosphate concentration did not differ between groups (p = 0.593). A weak positive relationship was demonstrated between FGF-23 and SDMA (r_S=0.34, p=0.001) and between FGF-23 and creatinine (r_S=0.23, p=0.03).

Cats with elevated SDMA had higher FGF-23 concentrations than those with SDMA within RI suggesting the presence of alteration in phosphate homeostasis despite no significant difference in plasma phosphate concentrations. Further studies are required to identify factors influencing this relationship and the utility of FGF-23 concentration to inform management of cats with early stage CKD.

Disclosures

Disclosures to report:

H.J. Sargent and Y.M. Chang have no conflicts of interest to declare. J. Elliott received funding from Consultancies: Elanco Ltd, CEVA Animal Health Ltd, Boehringer Ingelheim Ltd, Bayer Animal Health, Orion Incorp, Idexx Ltd, Nextvet Ltd, Waltham Centre for Pet Nutrition; grant funding from Elanco Ltd, Waltham Centre for Pet Nutrition, Royal Canin Ltd, Zoetis Ltd, CEVA Animal Health, Member of the International Renal Interest Society which receives a grant from Elanco Ltd. R. Jepson received funding from PetPlan, Feline Foundation for Renal Research, RVC Internal Grant, PetSavers, and consultancy agreements: Boehringer Ingelheim, Merial. Speaking honoraria: Boehringer Ingelheim, Hills Pet Nutrition.