Objective Evaluate urinary metabolites in cats that formed oxalate stones during life 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. Urinary samples were collected throughout life in annual physical exams and at the end of life. Urine was stored at -80 oC 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 635 analytes measured. There were 297 with different metabolite concentrations when the RD group was compared to the H group (six increased, 291 decreased). There were 202 metabolites with different concentrations when the CaOx group was compared to the H group (10 increased, 192 decreased). There were 55 with different concentrations between the CaOx group and the RD group with all of them being elevated in the CaOx group. Of interest in this group was the elevation of oxalate and a number of the purine family of bases (inosine, hypoxanthine, xanthosine, and urate). Oxalate concentration in the CaOx group was similar to H while inosine and hypoxanthine were elevated as compared to both H and RD groups. Lactate was reduced in the RD cats and unchanged in the CaOx cats when compared to H, resulting in a comparative increase of lactate in the CaOx vs RD groups while pyruvate was unchanged between all groups. Given that oxalate concentration in CaOx group was similar to H, these results indicate that there may be other molecular pathways including those involving purine metabolism that are involved in CaOx stone formation. Multifactorial nutritional strategies may need to be assessed for anti-urolithiatic activity, in addition to lowering oxalate to prevent stone formation. Conclusions The aberrant metabolism and excretion of purines in cats may be a significant component in the formation of calcium oxalate stone formation.
Read full abstract