Evaluation of Serum and Urine Amino Acids in Dogs with Chronic Kidney Disease and Healthy Dogs Fed a Renal Diet

This observational study aimed to evaluate serum and urinary amino acid (AA) concentrations in healthy dogs and dogs with chronic kidney disease (CKD) fed a commercial therapeutic renal diet with reduced protein and phosphorus levels. Ten dogs with CKD stages 3 or 4 composed the study group and received the renal diet for 180 days (RG T180). A control group (CG T30) composed of seven healthy dogs was fed a renal diet for 30 days. When comparing serum AA between RG T180 and CG T30, histidine, isoleucine, leucine, lysine, phenylalanine, tryptophan, cysteine, citrulline, ornithine, taurine, branched-chain amino acids (BCAA), and total essential amino acids (EAA) were higher in RG T180. Meanwhile, arginine, asparagine, aspartate, glutamine, serine, and tyrosine were higher in CG T30. Serum phenylalanine, tryptophan, and hydroxyproline were higher in RG T0 (dogs with CKD before consuming a renal diet) when compared to RG T180. In addition, the serum ratios of arginine/citrulline, tyrosine/phenylalanine, and serine/glycine were higher in CG T30 than in RG T180. Concerning urinary AA concentrations in CKD dogs, isoleucine, phenylalanine, tryptophan, aspartate, cysteine, and BCAA were higher in RG T180. In urine, the total EAA/total non-essential AA ratio in RG T180 was higher than in CG T30 as well as tyrosine/phenylalanine ratio higher in CG T30. In conclusion, the combination of renal diet and conservative treatment over 6 months in dogs with CKD stages 3 or 4 affected the AAs metabolism when compared to healthy adult dogs.

Healthy and Chronic Kidney Disease (CKD) Dogs Have Differences in Serum Metabolomics and Renal Diet May Have Slowed Disease Progression

Chronic kidney disease (CKD) is highly prevalent in dogs, and metabolomics investigation has been recently introduced for a better understanding of the role of diet in CKD. This study aimed to compare the serum metabolomic profile of healthy dogs (CG) and dogs with CKD (CKD-T0 and CKD-T6) to evaluate whether the diet would affect metabolites. Six dogs (5 females; 1 male; 7.47 ± 2.31 years old) with CKD stage 3 or 4 (IRIS) were included. CG consisted of 10 healthy female dogs (5.89 ± 2.57 years old) fed a maintenance diet. Serum metabolites were analyzed by 1H nuclear magnetic resonance (1H NMR) spectra. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to assess differences in metabolomic profiles between groups and before (CKD-T0) and after renal diet (CKD-T6). Data analysis was performed on SIMCA-P software. Dogs with CKD showed an altered metabolic profile with increased urea, creatinine, creatine, citrate, and lipids. Lactate, branched-chain amino acids (BCAAs), and glutamine were decreased in the CKD group. However, after 6 months of diet, the metabolite profiles of CKD-T0 and CKD-T6 were similar. Metabolomics profile may be useful to evaluate and recognize metabolic dysfunction and progression of CKD, and the diet may have helped maintain and retard the progression of CKD.

Study protocol: long-term effect of the New Nordic Renal Diet on phosphorus and lipid homeostasis in patients with chronic kidney disease, stages 3 and 4: a randomised controlled trial

IntroductionChronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. New Nordic Renal Diet (NNRD) is a new dietary concept designed by the present research group that aims to offer patients with moderate CKD a whole food approach with a markedly reduction in dietary phosphorus intake, corresponding to 850 mg/day. The present protocol describes a randomised controlled trial aiming to test the long-term effects of dietary intervention with NNRD versus a non-restricted habitual diet on important parameters of phosphorus and lipid homeostasis.Methods and analysisThis trial will be executed at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Sixty patients aged >18 years with CKD stages 3 and 4 (estimated glomerular filtration rate between 15 and 45 mL/min) will be recruited and randomly assigned to the intervention or control group. The other inclusion criterion includes a medically stable condition for at least 2 months prior to the start of the study. Exclusion criteria are treatment with phosphate binders, metabolic disorders that require specific dietary regulation, pregnancy and breast feeding, any types of food allergies or those who are vegans. The observation period is 26 weeks including seven study visits at the outpatient clinic combined with a weekly telephone consultation in both groups. A follow-up visit 3 months after study completion finalises the intervention. The primary outcome is the difference in the change in 24-hour urine phosphorus excretion from baseline to week 26 between the two study groups. Secondary outcomes include changes in phosphate-related and lipid metabolism-related blood and urine biochemistry, blood pressure and body composition. Moreover, we wish to explore adherence to the diet as well as quality of life.Ethics and disseminationThe study has been approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. The results of the studies will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals.Trial registration numberClinicalTrials.gov (wwwclinicaltrialsgov) Registry (NCT04579315).Protocol versionThe protocol, version 2, has been approved by the Ethical Committee Denmark on 18 September 2020. The protocol has also been approved by Data Protection Regulation and Data Protection Law on 15 September 2020. This study protocol is in accordance with the Standard Protocol Items: Recommendations for International Trials.

Plasma and urinary F2-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease

Objectives Oxidative stress contributes to chronic kidney disease (CKD) progression in humans and rodent models; F2-isoprostanes (F2-IsoPs) are established biomarkers of oxidative stress. Our primary aim was to evaluate plasma F2-IsoPs in cats with International Renal Interest Society stage 1 and 2 CKD, compared with healthy cats, and to determine whether plasma and urinary F2-IsoPs are equivalent biomarkers. The secondary aim was to assess whether consumption of a renal diet enriched in omega-3 fatty acids led to improvements in plasma and urinary F2-IsoPs. Methods Plasma and urinary F2-IsoPs were measured in 24 cats with stage 1 or 2 CKD, and 12 unaffected controls aged ⩾6 years. Twelve CKD cats were re-evaluated after feeding a commercial renal diet for at least 4 weeks. Results Median plasma F2-IsoPs were significantly higher in stage 1 CKD (96.2 pg/ml), early stage 2 CKD (83.2 pg/ml) and late stage 2 CKD (80.8 pg/ml) compared with healthy cats (22.8 pg/ml; P = 0.03−0.002). Median urinary F2-IsoPs were significantly higher in cats with stage 1 CKD (231.2 pg/mg) compared with healthy cats (152.5 pg/mg) or cats with late stage 2 CKD (124.8 pg/mg; P = 0.01). Plasma F2-IsoPs remained increased, while urinary F2-IsoPs fell with transition from stage 1 to stage 2 CKD. Feeding a commercial renal diet led to significant decreases in plasma F2-IsoPs in the small group of cats with stage 1 CKD (25−75% decrease) compared with cats with stage 2 CKD (20% decrease to 53% increase; P = 0.01). Conclusions and relevance Oxidative stress is prominent in cats with stage 1 CKD. Plasma and urinary F2-IsoPs are not interchangeable biomarkers in cats with stage 2 CKD. Placebo-controlled studies are indicated to evaluate dietary or pharmacologic doses of omega-3 fatty acids on redox stress and progression of renal dysfunction in cats with stage 1 CKD.

Diagnosis of the cat with early chronic kidney disease

Chronic kidney disease (CKD) is a highly prevalent disease and common cause of morbidity and mortality in older cats. Early diagnosis and management of CKD is thought to be able to slow disease progression and impact positively on quality of life and longevity. Dietary management with a therapeutic renal diet is regarded as the mainstay of treatment for feline CKD from International Renal Interest Society stage 2 onwards. However, since the advent of markers such as symmetric dimethylarginine that have enabled clinicians to detect non-azotaemic CKD, there has been growing debate about how to best manage these patients. At this stage there are a limited number of studies investigating this. This article covers the current diagnostics used to identify renal disease. A second article looks at current understanding of therapeutic strategies and the impact this can have on progression of the disease, focusing on dietary management.