Blood lactate concentration in diabetic dogs.

Human diabetic patients may have increased lactate levels compared to non-diabetics. Despite the use of lactate levels in critical care assessment, information is lacking for diabetic dogs. Therefore, this prospective cross-sectional clinical study aimed to determine lactate concentrations in 75 diabetic dogs [25 newly diagnosed non-ketotic diabetics, 25 under insulin treatment, and 25 in diabetic ketoacidosis (DKA)], compared to 25 non-diabetic dogs. Lactate levels (mmol/L) were not different among groups (P = 0.20); median and 25th to 75th percentile were 2.23 and P25-75 = 1.46 to 2.83 for controls, 1.69 and P25-75 = 1.09 to 2.40 for newly diagnosed non-ketotic diabetics, 2.27 and P25-75 = 1.44 to 2.90 for dogs under insulin treatment for at least 30 days, and 2.40 and P25-75 = 1.58 to 3.01 for dogs in DKA. Longitudinal studies assessing both isomers (L- and D-lactate) are needed to better elucidate the role of lactate in the pathophysiology of diabetes acid-base status in dogs.

La concentration de lactate de sang chez les chiens diabétiques. Des patients humains avec diabète peuvent présenter augmentation des niveaux de lactate, quand comparés aux non diabetiques. Bien que est utilisé d'évaluer les patients dans un état critique, cette information manque pour les chiens diabétiques. Par conséquent, cette étude clinique s'agit d'une prospective transversale en vue de detérminer les concentrations du lactate en 75 chiens diabétiques [25 au moment du diagnostic, 25 sous traitement à l'insuline et 25 dans l'acido-cétose diabétique (ACD)], par rapport aux 25 chiens non diabétiques. Les niveaux de L-lactate ne différaient pas entre les groupes (P = 0,20). Les valeurs médianes et les centiles 25 % et 75 % étaient de 2,23 mmol/L (P25­75 = 1,46 à 2,83) pour les contrôles, 1,69 mmol/L (P25­75 = 1,09 à 2,40) au diagnostic, 2,27 mmol/L (P25­75 = 1,44 à 2,90) sous traitement à l'insuline pendant au moins 30 jours, et 2,40 mmol/L (P25­75 = 1,58 à 3,01) dans ACD. Des études longitudinales évaluant les deux isomères (L et D-lactate) sont nécessaires pour élucider son rôle dans la physiopathologie et le déséquilibre acide-base chez les chiens diabétiques.(Traduit par Ana Carolina Possas Viana).

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)

Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis.

Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.

Hypervitaminosis A-induced hepatic fibrosis in a cat.

RATIONALE: The excessive intake of vitamin A in the form of vitamin concentrate, supplement or vitamin-rich liver can result in hypervitaminosis A in man and animals. Although osteopathologies resulting from chronic vitamin A intoxication in cats are well characterized, no information is available concerning feline hypervitaminosis A-induced liver disease. CLINICAL SUMMARY: We report the first case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat that had been fed a diet based on raw beef liver. Radiographic examination revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with deforming cervical spondylosis. Necropsy showed a slightly enlarged and light yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues revealed diffuse and severe liver fibrosis associated with hepatic stellate cell hyperplasia and hypertrophy. These cells showed immunopositive staining for α-smooth muscle actin and desmin markers. The necropsy findings of chronic liver disease coupled with osteopathology supported the diagnosis of hypervitaminosis A. PRACTICAL RELEVANCE: As in human hepatology, if there is dietary evidence to support increased intake of vitamin A, then hypervitaminosis A should be considered in the differential diagnosis of chronic liver disease in cats.

Avaliação da albuminúria e da eletroforese de proteínas urinárias de cães com hiperadrenocorticismo e a relação com a pressão arterial sistêmica / Evaluation of albminuria and electrophoresis of urinary proteins from dogs with hyperadrenocorticism and relation with systemic arterial pressure

O hiperadrenocorticismo é uma das endocrinopatias mais comuns em cães, sendo caracterizado pela exposição excessiva de glicocorticóides secretados pelas adrenais. A hipercortisolemia crônica pode promover várias complicações, incluindo hipertensão sistêmica e glomerulonefrite. A glomerulonefrite pode desencadear variáveis graus de proteinúria e uma tendência de evolução para doença renal crônica. A perda de proteínas na urina, principalmente da albumina, é uma característica das doenças glomerulares e a determinação de variáveis laboratoriais, como a razão proteína:creatinina urinária (RPC), albuminúria (teste de ELISA) e eletroforese das proteínas urinárias, são recomendadas para a elucidação do diagnóstico. Assim, o objetivo do estudo é avaliar a relação entre proteinúria e hipertensão arterial sistêmica em cães com hiperadrenocorticismo e verificar, pela avaliação da albuminúria e do peso molecular das proteínas urinárias, o segmento do néfron que foi comprometido ou lesado. Foram avaliados 30 cães com diagnóstico de hiperadrenocorticismo, subdivididos em 13 cães com hipertensão arterial sistêmica (grupo I) e 17 cães normotensos (grupo II). Foram determinados a RPC; a albuminúria pela avaliação da albumina normalizada e razão albumina:creatinina urinária (RAC) e a eletroforese de proteínas pela técnica em gel de poliacrilamida, contendo dodecil sulfato de sódio (SDS-PAGE). Os resultados foram comparados com os dados obtidos de 30 cães clinicamente saudáveis. Foi constatado que não houve influência da hipertensão arterial sistêmica nos cães com hiperadrenocorticismo em relação à quantificação da albuminúria, determinada pelo método ELISA, e nem na qualidade e quantidade das bandas de proteínas de baixo (<60 kDa) e de alto peso molecular (>60 kDa). No entanto foi determinado que cães com hiperadrenocorticismo podem desenvolver lesões glomerulares e tubulares, caracterizadas pela presença de albuminúria e de proteínas de alto e de baixo pesos moleculares, independentemente da presença de hipertensão arterial sistêmica. Conclui-se que a avaliação quantitativa (RPC e RAC) e qualitativa (SDS-PAGE) das proteínas urinárias traz informações adicionais que indicam os possíveis segmentos comprometidos dos néfrons que causaram as perdas de proteínas na urina.

Hyperadrenocorticism is one of the commonest endocrinopathies in dogs, and it is characterized by the excessive exposure of glucocorticoids excreted by adrenals. Chronic hypercortisolemia may promote several complications, including systemic hypertension and glomerulonephritis. Glomerulonephritis may initiate several variable degrees of proteinuria and leading to the development of chronic kidney disease. The loss of proteins through urine, mainly predominant albumin, is a characteristic of glomerular diseases and the determination of laboratorial variables, such as the urinary protein-to- creatinine ratio (UPC), urinary albumin-to-creatinine ratio (UAC; ELISA test) and electrophoresis of urinary proteins are recommended to elucidate the diagnosis. Therefore, the goal of this study is to evaluate the relationship between proteinuria and systemic arterial hypertension in dogs with hyperadrenocorticism and to determine through evaluation of albuminuria and molecular weight of urinary proteins, the segment of the nephron that could be damaged. Thirty dogs with hyperadrenocorticism were evaluated and subdivided into groups; 13 dogs with systemic arterial hypertension (group I) and 17 normotensive (group II). The UPC was determined, as well as UAC and the urine protein electrophoresis by polyacrylamide gel technique, containing dodecyl sodium sulphate (SDS-PAGE). The results were compared with data obtained from 30 clinically healthy dogs. No association between systemic arterial hypertension and albuminuria was detected in dogs with hyperadrenocorticism as well as no alterations of proteins patterns or molecular weights bands of low (<60 kDa) or high molecular weight (> 60 kDa) was found. However, dogs with hyperadrenocorticism may develop glomerular and tubular injuries that were characterized by the presence of albuminuria and proteins of low and high molecular weights, independently of systemic arterial hypertension. In conclusion, the quantitative (UPC and UAC) and qualitative (SDS-PAGE) evaluation of urinary proteins could add information to indicate the possible segments of the nephrons that caused the loss of those proteins.

Serum intact parathyroid hormone levels in cats with chronic kidney disease / Avaliação das concentrações séricas de paratormônio intacto em gatos com doença renal crônica

Chronic kidney disease (CKD) is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT) is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS) as Stage II (n=12), Stage III (n=22) and Stage IV (n=6). Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH) concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

A doença renal crônica (DRC) em gatos é frequentemente observada e caracteriza-se como alteração multissistêmica, causada por alterações metabólicas, e o hiperparatireoidismo secundário renal (HPTSR) seria o mais comum e usualmente está associada com progressão da doença renal e mau prognóstico. Esse estudo teve como objetivo determinar a frequência do HPTSR, e discutir os possíveis mecanismos que podem contribuir para o desenvolvimento de SRHPT em gatos em diferentes estágios de DRC, pela avaliação do metabolismo do cálcio e fósforo, bem como do equilíbrio ácido-base. Quarenta gatos com DRC foram divididos em três subgrupos, de acordo com a classificação proposta pela International Renal Interest Society (IRIS), Estágio II (n=12), Estágio III (n=22) e Estágio IV (n=6). O grupo-controle foi composto por 21 gatos clinicamente saudáveis. O aumento das concentrações séricas de paratormônio intacto (PTHi) foi observado na maioria dos casos, mas principalmente no Estágio IV, no qual a hiperfosfatemia e a hipocalcemia ionizada parecem estar associadas ao desenvolvimento do HPTSR. No entanto, nos Estágios II e III, observou-se hipercalcemia ionizada, sugerindo que, nestes estágios, o desenvolvimento do HPTSR possa estar associado a outros fatores, e a acidose metabólica pode estar envolvida com o desenvolvimento de hipercalcemia ionizada. Assim, outros fatores, além da hiperfosfatemia e da hipocalcemia ionizada, possam estar envolvidos com o desenvolvimento do HPTSR, principalmente nos estágios iniciais da DRC. Futuros estudos são necessários para uma melhor compreensão da fisiopatologia do HPTSR em gatos.

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease.

BACKGROUND: Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). OBJECTIVE: The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. METHODS: Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. RESULTS: UAC in dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC 0.03-0.3) and macroalbuminuria (UAC>0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure > or =180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure<180 mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC>1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had microalbuminuria, and those with UPC<0.5 usually lacked albuminuria. CONCLUSIONS: UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC < or = 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Evaluation of albuminuria and its relationship with blood pressurein dogs with chronic kidney disease

Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD).The objective of this study was to evaluate albuminuria and itsassociation with arterial hypertension in dogs with CKD.Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine(UPC) ratio, and systolic blood pressure were determined in 39 clinicallyhealthy dogs and 40 dogs with CKD.UAC in dogs with CKD (range, 0.002–7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005–0.01; median, 0.002). Microalbuminuria (UAC 0.03–0.3) and macroalbuminuria(UAC40.3) were detected in 32.5% and 50% of dogs with CKD, respectively.Sixty percent (24/40) of dogs with CKD had systolic pressure Z180 mmHg; in these dogs, UAC ratio (range, 0.006–7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure o180mmHg (range, 0.002–4.83; median, 0.10). Of hypertensive dogswith CKD, those with UPC41.0 usually had macroalbuminuria, those with UPC 0.5–1.0 usually had microalbuminuria, and those with UPCo0.5 usually lacked albuminuria.UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Accuracy of serum beta-hydroxybutyrate measurements for the diagnosis of diabetic ketoacidosis in 116 dogs.

The aim of this study was to evaluate the accuracy of serum beta-hydroxybutyrate (beta-OHB) measurements for the diagnosis of diabetic ketoacidosis (DKA) in dogs. One hundred sixteen diabetic dogs were prospectively enrolled in the study: 18 insulin-treated (IT) diabetic dogs that had a positive urine ketone test and 88 untreated, newly diagnosed diabetic dogs. Venous blood gas tensions and pH, serum glucose and urea nitrogen (SUN), and electrolyte (Na+, Cl-, and K+) and urine acetoacetate (AA) concentrations were measured concurrently with serum beta-OHB concentrations. On the basis of laboratory findings, the patients were assigned to I of 3 groups: diabetic ketoacidosis (n = 43); diabetic ketosis (DK, n = 41); and nonketotic diabetes (NDK, n = 31). Serum beta-OHB concentrations differed significantly (P < .001) among the study groups. Although marked differences in beta-OHB concentrations were found, a considerable overlap exists between the distributions of dogs with DK and those with DKA. The overall accuracy of beta-OHB determination as a diagnostic test for DKA, determined by the area under the receiver operating characteristic (ROC) curve, was 0.92. In the 1.9- to 4.8-mmol/L range, serum beta-OHB determination sensitivity varied from 100 to 35.7%, whereas specificity varied from 39 to 100%. The cutoff value of 3.8 mmol/L showed the best equilibrium between specificity (95%), sensitivity (72%), and likelihood ratio (14.8). We concluded that the quantitative measurement of serum beta-OHB may be a potential tool for diagnosing and monitoring ketosis and ketoacidosis in diabetic dogs.