Participants and study design
Two studies were conducted to evaluate the effect of naturally occurring dietary ingredients on kidney health (Fig 1). The first study was a crossover trial with seven CKD cats. All cats were fed either test food or control food for 8 weeks and then were crossed over to the other food for 8 weeks. The study used a pre-trial food (control food) and a test food that contained betaine and prebiotics: long-chain oat beta-glucan and short-chain fructo-oligosaccharides (scFOSs). The second study was a randomized study with 16 healthy cats assigned to control or test food. Each group of eight cats received control or test food for 8 weeks. Control and test food were the same in both studies.
The pre-trial food (control food) was a complete and balanced dry food designed to aid in the management of CKD. Test food was the pre-trial food supplemented with betaine (0.500%) and prebiotics: oat beta-glucan (0.586%) and scFOS (0.407%). The CKD cats were fed pre-trial food for 4 weeks in study one and then were randomly assigned to control food or test food in a cross-over study design. In the second study, all 16 healthy cats were fed the pre-trial food for one week, as an independent study showed that one week was an adequate wash out period in healthy cats fed test food similar to their off-test food [19]. The cats were then randomly assigned to the control food (eight cats) or the test food (eight cats). Healthy cats received control food or test food for 8 weeks. Because the total number of cats in the second study was greater, a cross-over study was not needed. All cats had access to electronic feeders whereby fresh food was offered daily with amounts available for consumption calculated to maintain body weight; water was available ad libitum. Actual daily food intake (g/day) was recorded for each cat.
All cats were of domestic shorthair breed. At baseline, cats in the CKD study ranged in age from 6.0 to 16.2 years, and body weights ranged from 3.8 to 7.1 kg. There were four spayed females and three neutered males. Inclusion criteria were cats with CKD or kidney stones. Cats were considered reasonable to have CKD if one or more of these diagnostic findings were observed: 1) persistently increased serum creatinine (Cr ≥1.6 mg/dL), 2) persistently increased serum symmetric dimethylarginine (SDMA > 14 μg/dL), or 3) persistently dilute urine specific gravity (USG ≤ 1.030) without identifiable non-renal cause. This included cats with CKD (IRIS stages 1 and 2; n = 3; one had kidney stones), cats with kidney stones (n = 3), and one cat with a missing right kidney. Cats with CKD were assigned IRIS stage at baseline based on the results of an annual physical examination, complete blood count (CBC), serum biochemistries, and urinalysis [20]. Cats were excluded from the group if they were known to have problems eating new foods or problems with repeat blood sampling, and/or had any other diagnosed disease condition such as diabetes, cancer, inflammatory bowel disease, dermatitis, or food allergy. Cats in the second study were healthy cats of ideal body weight and with no evidence of CKD or other diseases. Cats were determined to be healthy based on the results of an annual physical examination, CBC, serum biochemistries, and urinalysis. At baseline, healthy cats ranged in age from 2.6 to 9.3 years, and body weights ranged from 3.2 to 5.8 kg. There were 11 spayed females and five neutered males. The criterion for removal from either study was development of any condition whereby removal would benefit the animal, including any cat refusing to eat, or inadequate food intake resulting in weight loss greater than 15% of body weight. No cats were removed from either study.
Blood, urine, and fecal samples were collected at baseline (end of pre-trial period) and at the end of each 8-week feeding period to evaluate changes in plasma, urine, and fecal metabolites in CKD cats. Assays also included CBC, serum biochemical analysis, urinalysis, and urine protein/creatinine (UPC) ratio. Body weight and composition were measured using dual-energy X-ray absorptiometry (DEXA) scan at baseline and after each feeding period. For healthy cats, blood was collected at baseline, at one month into the feeding trial, and at the end of the eight-week feeding period.