Metabolomic changes in cats with renal disease and calcium oxalate uroliths

Abstract

Introduction There is a significant incidence of cats with renal disease (RD) and calcium oxalate (CaOx) kidney uroliths in domesticated cats. Foods which aid in the management of these diseases may be enhanced through understanding the underlying metabolomic changes. Objective Assess the metabolomic profile with a view to identifying metabolomic targets which could aid in the management of renal disease and CaOx uroliths. Method This is a retrospective investigation of 42 cats: 19 healthy kidney controls, 11 with RD, and 12 that formed CaOx nephroliths. Cats were evaluated as adults (2 through 7 years) and at the end of life for plasma metabolomics, body composition, and markers of renal dysfunction. Kidney sections were assessed by Pizzolato stain at the end of life for detection of CaOx crystals. CaOx stone presence was also assessed by analysis of stones removed from the kidney at the end of life. Results There were 791 metabolites identified with 91 having significant (p < 0.05, q < 0.1) changes between groups. Many changes in metabolite concentrations could be explained by the loss of renal function being most acute in the cats with RD while the cats with CaOx stones were intermediate between control and RD (e.g., urea, creatinine, pseudouridine, dimethylarginines). However, the concentrations of some metabolites differentiated RD from CaOx stone forming cats. These were either increased in the RD cats (e.g., cystathionine, dodecanedioate, 3-(3-amino-3-carboxypropyl) uridine, 5-methyl-2′-deoxycytidine) or comparatively increased in the CaOx stone forming cats (phenylpyruvate, 4-hydroxyphenylpyruvate, alpha-ketobutyrate, retinal). Conclusions The metabolomic changes show specific metabolites which respond generally to both renal diseases while the metabolomic profile still differentiates cats with RD and cats with CaOx uroliths.

Untargeted metabolomic profiling of serum from client-owned cats with early and late-stage chronic kidney disease

“…Although these lipid metabolites were only weakly-correlated with clinical and laboratory parameters (Supplementary File 3), the roles that lipid metabolism plays in CKD, especially in its progression from early-stage to late-stage disease, are largely unknown 26 , 28 , such that their levels in serum may increase or decrease via mechanisms that are not proportionate to conventional monitoring parameters. Similar to this study, robust changes to lipid metabolism were identified in the plasma metabolome of purpose-bred research cats by both Hall et aland Jewel et al, where cats with CKD showed alterations to multiple fatty acids including phospholipids, ceramides, and dicarboxylates when compared to healthy cats 9 , 10 . In turn, both increases and decreases in serum lipid metabolites should be considered as biologically meaningful changes in cats with CKD.…”

“…Various feline untargeted metabolomics studies have been performed 8 – 12 . The studies used plasma 9 , 10 , serum 11 , feces 8 , 9 , and urine 12 collected from cats with early-stage CKD. Most studies used purpose-bred research cats 8 – 11 and examined dietary impacts on the metabolome 8 , 9 , 11 .…”

Gut and Urinary Microbiota in Cats with Kidney Stones

“…[ 78 ], it is now necessary to consider that urinary bacteria are also involved in the formation of calcium oxalate stones, with the exact mechanism yet to be elucidated. The urinary microbiota could act by altering the urine pH, producing metabolites that influence the solubility of minerals in the urine, interacting with substances like citrate that inhibit stone formation, increasing oxalate concentration, or serving as nuclei for mineral crystallization [ 22 , 31 , 64 , 79 , 80 , 81 ].…”

Untargeted metabolomic profiling of serum from client-owned cats with early and late-stage chronic kidney disease

“…This method has been extensively performed in people with CKD and was successfully used for biomarker discovery for early diagnosis and etiology identi cation [7]. Various feline untargeted metabolomics studies have been performed [8][9][10][11][12]. The studies used plasma [9,10], serum [11], feces [8,9], and urine [12] collected from cats with early-stage CKD.…”

“…Various feline untargeted metabolomics studies have been performed [8][9][10][11][12]. The studies used plasma [9,10], serum [11], feces [8,9], and urine [12] collected from cats with early-stage CKD. Most studies used purpose-bred research cats [8][9][10][11] and examined dietary impacts on the metabolome [8, 9,11].…”