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.

Evaluation of Electrolyte Concentration and Pro-Inflammatory and Oxidative Status in Dogs with Advanced Chronic Kidney Disease under Dietary Treatment.

An integrated study on the effect of renal diet on mineral metabolism, fibroblast growth factor 23 (FGF-23), total antioxidant capacity, and inflammatory markers has not been performed previously. In this study, we evaluated the effects of renal diet on mineral metabolism, oxidative stress and inflammation in dogs with stage 3 or 4 of chronic kidney disease (CKD). Body condition score (BCS), muscle condition score (MCS), serum biochemical profile, ionized calcium (i-Ca), total calcium (t-Ca), phosphorus (P), urea, creatinine, parathyroid hormone (PTH), FGF-23, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and total antioxidant capacity (TAC) were measured at baseline (T0) and after 6 months of dietary treatment (T6). Serum urea, P, t-Ca, i-Ca, PTH, FGF-23, IL-6, IL-10, TNF-α and TAC measurements did not differ between T0 and T6. Serum creatinine (SCr) was increased at T6 and serum PTH concentrations were positively correlated with serum SCr and urea. i-Ca was negatively correlated with urea and serum phosphorus was positively correlated with FGF-23. Urea and creatinine were positively correlated. The combination of renal diet and support treatment over 6 months in dogs with CKD stage 3 or 4 was effective in controlling uremia, acid-base balance, blood pressure, total antioxidant capacity, and inflammatory cytokine levels and in maintaining BCS and MCS.

Urinary Fractional Excretion of Phosphorus in Dogs with Spontaneous Chronic Kidney Disease.

The increase of urinary fractional excretion of phosphorus (uFEP) may indicate phosphorus retention before the onset of hyperphosphatemia in the early stages of chronic kidney disease (CKD). The hypothesis of this study is whether uFEP may increase during the early stage of CKD as a compensatory mechanism to prevent hyperphosphatemia as well as whether hyperphosphatemia in the late stages is associated with increase or decrease in uFEP in dogs with naturally occurring CKD; therefore, the aim of this study was to determine the uFEP in CKD dogs with different stages. Forty-nine CKD dogs were included, and they were divided into stage 1 (serum creatinine < 1.4 mg/dL), stage 2 (serum creatinine 1.5 to 2.0 mg/dL), stage 3 (serum creatinine 2.1 to 5.0 mg/dL) and stage 4 (serum creatinine > 5.0 mg/dL), according to the IRIS staging criteria. The stage 3 was subdivided into stage 3-A (serum creatinine 2.1 to 3.5 mg/dL) and stage 3-B (serum creatinine 3.6 to 5.0 mg/dL). The control group comprised 10 dogs, and uFEP ≤ 40% was considered as normal. A progressive increase in uFEP along the progression of CKD was found. However, similar results of uFEP levels were observed in late CKD, since there were no differences between stages 3 (A, B) and 4. Interestingly, some CKD dogs with stage 4 showed normal or reduced uFEP, besides hyperphosphatemia; conversely, some dogs in early CKD had increased uFEP values and normophosphatemia. Our findings suggest that uFEP may act as a compensatory mechanism to avoid the onset of hyperphosphatemia in early CKD, but not in later stages. uFEP assessment may be considered as an additional tool for the diagnostic and monitoring of phosphate disorders in dogs with CKD, since it may help to identify disturbances of phosphorus balance. More studies are needed to elucidate the role of uFEP in phosphorus homeostasis in dogs with CKD.

Urine protein electrophoresis study in dogs with pituitary dependent hyperadrenocorticism during therapy with trilostane / Avaliação da proteína urinária por eletroforese em cães com hiperadrenocorticismo hipófise dependente durante a terapia com trilostano

Hyperadrenocorticism is one of the most common endocrine disorders in dogs. Regarding to the kidneys, chronic hypercortisolemia can cause damage to the glomerulus, and evolve into chronic kidney disease. This study evaluated nine normotensive dogs with pituitary dependent hyperadrenocorticism, before and after therapy with trilostane, during the follow-up period of six months, in order to investigate the development of pathological proteinuria by quantitative (urinary protein-to-creatinine ratio) and qualitative (urinary protein electrophoresis) methods, and also to monitor its intensity over the course of the disease and therapy. The main renal lesion detected in dogs with hyperadrenocorticism was in the tubular segment, evidenced by the prevalence of urinary protein bands of lower molecular weight, indicating the lack absorption of these proteins in the proximal segment of the nephron. Low molecular weight proteins persisted throughout the follow-up. Regarding the future of routine veterinary medical clinic in the care of patients with hyperadrenocorticism, the assessments of proteinuria determinations by the urinary protein-to-creatinin ratio and urinary protein electrophoresis, according to the results obtained in this study, can add more information about the renal damage in these animals, and contribute to the prognosis.(AU)

Hiperadrenocorticismo (HAC) é uma das doenças endócrinas mais comuns em cães. A hipercortisolemia crônica pode causar danos glomerulares, pelo aumento da taxa de filtração glomerular, podendo levar ao desenvolvimento de doença renal crônica. Este estudo avaliou nove cães normotensos com hiperadrenocorticismo hipófise-dependente, antes e após a terapia com trilostano, durante o período de acompanhamento de seis meses, a fim de investigar o desenvolvimento de proteinúria patológica por métodos quantitativo (relação proteína e creatinina urinária) e qualitativos (eletroforese de proteínas urinárias) e também para monitorar a sua intensidade ao longo do curso da doença e terapia. A principal lesão renal detectada em cães com HAC foi no segmento tubular, evidenciada pela prevalência de bandas de proteínas urinárias de peso molecular mais baixo, indicando a falta de absorção destas proteínas no segmento proximal do néfron. A proteinúria de baixo peso molecular persistiu durante todo o acompanhamento. Em relação ao futuro da rotina clínica médica veterinária no tratamento de cães com hiperadrenocorticismo, as avaliações de proteinúria pela relação proteína e creatinina urinária e eletroforese de proteínas urinárias, de acordo com os resultados obtidos neste estudo, podem adicionar mais informações sobre a lesão renal nestes animais e contribuir para o prognóstico.(AU)

Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein, and retinol-binding protein as early biomarkers of chronic kidney disease in dogs.

Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein-to-creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS-PAGE and western blotting to determine the expression of albumin, vitamin D-binding protein (VDBP), retinol-binding protein (RBP), and Tamm-Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (n = 9); and dogs with CKD (n = 40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (P ≤ 0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (P ≤ 0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

Evaluation of oxidative stress in the anemia of dogs with chronic kidney disease.

BACKGROUND: Anemia and systemic oxidative stress may occur in dogs with chronic kidney disease (CKD). Only scarce information regarding the intraerythrocytic redox status under these conditions is available at this time. OBJECTIVE: The aim of this study was to evaluate the indicators of oxidative stress and intraerythrocytic antioxidant defense in dogs with anemia of CKD. METHODS: Thirty dogs with CKD in stages 3 or 4 with nonregenerative anemia (HCT ≤ 37%) were compared to 20 healthy dogs. Complete blood count, reticulocyte %, blood smear evaluation, intraerythrocytic concentrations of total (GSHt), reduced (GSH), and oxidized glutathione (GSSH), and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase (SOD), as well as plasma concentrations of thiobarbituric acid-reactive substances (TBAR) were determined. RESULTS: Anemia of CKD dogs was nonregenerative (reticulocytes ≤ 0.2% with scarce anisocytosis and poikilocytosis). Intraerythrocytic GSSH and SOD, and plasma TBAR were higher in dogs with CKD. There was a positive correlation between the creatinine concentration and TBAR, and negative correlations between creatinine concentration and HCT, as well as between HCT and TBAR. In CKD dogs with a higher degree of anemia, SOD levels were higher and GSSH concentrations were lower. Despite the evidence of increased systemic oxidative stress, the compensatory response of SOD and the sustained intraerythrocytic concentrations of GSSH in CKD dogs with anemia indicated that the erythrocytes maintained the antioxidant defense. CONCLUSIONS: There was no strong evidence that oxidative stress was associated with higher degrees of anemia in dogs with CKD.