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.

Chronic low-grade inflammation is a key contributor to the progression of kidney disease. The release of cytokines and other pro-inflammatory proteins may further contribute to detrimental kidney health by increasing interstitial edema and renal fibrosis. The aim of the present study was to investigate the inflammatory markers in canines who developed renal disease naturally and were diagnosed with renal disease either during life or following necropsy, as assessed by a veterinarian. RNA was isolated from canine blood obtained at necropsy and stored as bioarchived samples from ten canines with renal disease (9.6–14.7 yr) and ten controls (10.1–14.8 yr). At the time of death, the mean blood creatinine concentration and BUN were elevated in dogs with renal disease compared to control (both p < 0.01). Samples were assessed for changes in gene expression using the Canine cytokine RT2 Profiler PCR Array for inflammation. There was a significant increase in C-C Motif Chemokine Ligand 16 (CCL16), C-X-C Motif Chemokine Ligand 5 (CXCL5), Interleukin 16 (IL-16), and Complement Component 5 (C5) (all p < 0.05 vs. con). In addition, there was also a statistically non-significant increase in 49 genes and a down-regulation in 35 genes from a panel of total 84 genes. Pro-inflammatory genes including CCL16, CXCL5, IL-16, and C5 can all contribute to renal inflammation and fibrosis through different signaling pathways and may lead to a progressive impairment of kidney function. Blockade of their activation may be important in ameliorating the initiation and/or the progression of renal disease.

The Mediterranean diet is characterized by an increased consumption of fruits, vegetables, grains, and fish. Olive oil and herbs and spices are also essential components of this food regimen. Such a diet is associated with a reduced risk of cardiovascular disease, overall mortality, reduced incidence of Parkinson’s and Alzheimer’s diseases, and reduced cognitive impairment. Some of the bioactive components that exert beneficial effects are ω-3 fatty acids, polyphenols, and alkaloids that have neuroprotective, anti-inflammatory, antioxidant, antimicrobial, and gluco-regulating properties. These beneficial effects contribute to improved health including organ health and cognitive function. While the number of such bioactive plant constituents is numerous, this review will examine the role of specific bioactives and vitamins and assess the molecular mechanisms including the antioxidant and anti-inflammatory beneficial effects of the bioactive components in the Mediterranean diet.

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Ketogenic foods (KF) limit digestible carbohydrate but contain high fat, and have antioxidant and anti‐inflammatory effects as well as improving mitochondrial function. Beta hydroxybutyrate (BHB), one of the ketone bodies, has been reported to reduce pro‐inflammatory NLRP3 inflammasome, as well chemokines including CXCL2 and CCL5 in cultures. We assessed the immune‐modulating effects of two low carbohydrate (LoCHO) foods varying in protein and fat, and compared their effects to a food replete with carbohydrate (CON) in healthy canines. This study was approved by IACUC and the Animal Welfare Committee, Hills PNC. Macronutrients (P/F/C; % energy) for the foods were: CON (23/34/35), LoCHO1 (53/39/8) and LoCHO2 (27/67/5). We previously reported that LoCHO2 significantly increased circulating BHB compared to both CON and LoCHO1 although LoCHO1 did not increase BHB above that found when dogs consumed CON food. In the present study, dogs were fed control food (CON; ketogenic ratio (KR 0.46) followed by LoCHO1 (KR: 0.97), then LoCHO2 (KR: 1.63) or LoCHO2 followed by LoCHO1. Each food was fed for 5 weeks, with collections in the 5th week; 15 weeks feeding total. Gene expression for inflammatory cytokines and receptors from whole blood collected in PAXgene RNA tubes from 10 dogs was assessed using Canine RT2 Profiler PCR array. When compared to CON there was a significant decrease in several pro‐inflammatory cytokines/chemokines in both LoCHO1 and LoCHO2 groups including CCL1, CCL8, CCL13, CCL17,CCL24, CX3CL1, CXCR1, IL‐10RA, IL‐17A, IL‐1RN, IL‐5, IL‐9, and SPP1 (all p<0.05). Interestingly, a subset of inflammatory proteins that decreased in LoCHO1, but not in LoCHO2, included IL‐33, IL‐6R, Il‐7, IL‐8, NAMPT, and TNFRSF11B. In contrast, the decrease in inflammatory markers in LoCHO2, but not in LoCHO1, included C5, CSF3, IFN‐γ, IL‐3, IL‐10RB, IL‐17C, TNFSF13, TNFSF13B, and TNFSF14. Decreased levels of selected cytokines indicate the ability of both low‐carbohydrate foods to exert an anti‐inflammatory effect and provide a strong rationale for testing its efficacy in dogs with inflammatory conditions. For instance, cytokines including IL‐7 and IL‐8 are increased in chronic inflammatory conditions such as colitis, dermatitis, as well as in autoimmune conditions. Increased IL‐33 is also associated with chronic lesional skin of atopic dermatitis in canines and these conditions might benefit from LoCHO1 food. LoCHO2 food decreased complement component 5 (C5) and blockade of C5 attenuates renal dysfunction including glomerulopathy. LoCHO2 also decreased TNFSF13, a member of the tumor necrosis factor superfamily, highly expressed in tumors, and associated with poor prognosis, indicating its potential as a nutritional intervention strategy for cancer. Taken together, our results indicate that both LoCHO1 and LoCHO2 foods might be important as part of immune‐modulating therapeutic nutritional strategies to reduce inflammation or inflammatory pathways to maintain health in canines.