Cats with calcium oxalate stones and renal disease have different plasma metabolome when compared to cats with healthy renal function

Objective Evaluate the effect of cats that formed oxalate stones during life on plasma metabolite concentration as compared to cats with healthy kidneys or cats with chronic kidney disease. Methods The development and end of life effects of renal disease and calcium oxalate stone formation was evaluated with 42 cats evaluated from one year of age to end of life (21 spayed females and 21 neutered males). Each cat was assigned to one of three groups: calcium oxalate stone forming cats (CaOx, n=12, confirmed by stone analysis), cats with renal disease (RD, n=11) and healthy kidney cats (H, n=19). Their condition was defined during life or at the time of death. Plasma samples were collected throughout life in annual physical exams and at the end of life. Plasma was stored at ‐80 o C until analyzed. Metabolomic analysis was completed by Metabolon (Durham, NC). Statistical analysis was completed on natural log transformed data using group as an independent variable, animal age as a continuous variable, and each cat as a random variable. A statistical cutoff of p<0.05 was used. Results There were 789 analytes measured. There were 144 metabolites with different concentrations when the RD group was compared to the H group (112 increased, 32 decreased). There were 130 with different concentrations when the CaOx group was compared to the H group (116 increased, 14 decreased). There were 69 with different concentrations between the CaOx group and the RD group (47 increased, 32 decreased. Both RD and CaOx had increased concentrations in circulating analytes known to increase with reduced renal function (creatinine, urea, pseduouridine). The CaOx cats had higher levels of 1‐palmitoyl‐GPI, 1‐stearoyl‐GPI, and mannitol/sorbitol when compared to the RD cats. The RD cats had higher levels of guanosine, guanine, inosine and hypoxanthine when compared to the CaOx cats. These higher levels was the result of increases in the RD cats and reduced concentrations in the CaOx cats (when compared to H). Conclusions The aberrant metabolism and clearance of purines in cats may be a significant component in the formation of calcium oxalate stone formation.