Clarifying expression patterns by renal lesion using transcriptome analysis and vanin-1 as a potential novel biomarker for renal injury in chickens.

Bird death is often caused by renal lesions induced by chemicals. The avian kidney has a renal portal system with significant blood flow that is sensitive to many chemicals. However, early avian biomarkers for kidney injury are yet to be identified. This study aimed to identify novel renal biomarkers. Acute kidney injury (AKI) can be divided into acute interstitial nephritis (AIN) and acute tubular necrosis (ATN). A chicken model of kidney damage was created by an injection of diclofenac or cisplatin, which caused either AIN or ATN, respectively. Microarray analysis was performed to profile the gene expression patterns in the chickens with nephropathy. A gene enrichment analysis suggested that the genes related to responses to external stimuli showed expression changes in both AIN and ATN. However, hierarchical clustering analyses suggested that gene expression patterns differed between AIN and ATN, and the number of biomarkers relating to renal damage was low. To identify early biomarkers for nephropathy, we focused on genes that were induced at various levels of renal damage. The gene, vanin-1 (VNN1) was highly induced in the early stages of renal damage. A quantitative real-time PCR analysis supported this finding. These results suggest VNN1 could be a useful early biomarker of kidney injury in avian species.

Histopathological kidney changes and myoglobinuria in neotropical non-human primates attacked by dogs, Brazil.

BACKGROUND: Non-human primates (NHPs) are susceptible to dogs' attacks, events that may cause muscle damage along with stress, and could be in some extent compatible with capture myopathy, a syndrome that results in myoglobinuria and renal damage. METHODS: We aimed to evaluate by histopathology pre-existing lesions and subsequent sequelae related to dogs' attacks, acute tubular necrosis (ATN) and myoglobinuria, as well as the usefulness of Pearls Stain and IHC to diagnose it. Histopathology was performed in available organs, and sections of kidney submitted to Prussian blue stain and myoglobin immunohistochemistry. RESULTS: During January 2014-June 2016, 16/145 (11%) of NHPs received by Adolfo Lutz Institute, Brazil were reported as attacked by dogs. A high frequency of young and debilitated animals was found. Myoglobinuria was observed in more than half animals (9/16; 56.2%), from which (5/9; 55.5%) presented ATN. CONCLUSIONS: Kidney lesions are plausible findings in NHPs attacked by dogs.

Histological evaluation and E-cadherin and ß-catenin expression in kidney of dogs submitted to renal ischemia and reperfusion after chlorpromazine administration / Avaliação histológica e imunomarcação de E-caderina e ß-catenina em rins de cães submetidos a isquemia e referfusão renal após administração de clorpromazina

Renal ischemia can be associated with some urological procedures, such as renovascular surgery or kidney transplantation, that are often followed by acute renal failure. The aim of this study was to verify the E-cadherin and ß-catenin localization in canine kidney in different times of renal ischemia and reperfusion after chlorpromazine application. Twelve dogs were randomly distributed equally into two groups. GroupA with ischemia and reperfusion without chlorpromazine and groupB with ischemia and reperfusion treated by chlorpromazine. GroupB received intravenous chlorpromazine, 15 min before the artery obstruction, which lasted 1 hour. After this period, the clamps in the renal arteries were released and the organ remained in reperfusion for 2 hours. In each group, anti-E-cadherin and anti-ß-catenin antibodies were made in six tissue samples from renal parenchyma. E-cadherin and ß-catenin are differentially expressed in segments from cortex and medulla in dog's kidneys and the use of chlorpromazine did not alter the expression of both proteins. Occlusion of the left renal artery in dogs causes morphological alterations mainly in proximal convoluted tubules, beginning 30min after the start of ischemia and being aggravated after two hours of reperfusion. These results reveal that chlorpromazine did not change kidneys' histological aspect nor E-cadherin and ß-catenin expression.(AU)

A lesão renal isquêmica pode estar associada a procedimentos urológicos, tais como cirurgia renovascular, cirurgia renal extracorpórea ou transplante renal. Essa injúria, muitas vezes, é seguida de insuficiência renal aguda. O objetivo deste trabalho foi observar a localização da E-caderina e da ß-catenina em rim de cães, além de relacionar a expressão dessas proteínas das junções de aderência em diferentes tempos de isquemia e reperfusão com ou sem a aplicação de clorpromazina. Para tanto, foram utilizados 12 cães, distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A, com isquemia e reperfusão sem tratamento por clorpromazina, e o grupo B, com isquemia e reperfusão tratado por clorpromazina. No procedimento cirúrgico, foi realizada uma incisão paracostal esquerda para identificação e isolamento do rim esquerdo e da artéria renal esquerda. Após o isolamento da artéria, os animais de todos os grupos tiveram o vaso ocluído. Os animais do grupo B receberam clorpromazina via endovenosa, na dose de 5mg/kg, 15min antes da clampagem do vaso, que durou uma hora. Após este período, as artérias renais foram desobstruídas e os órgãos permaneceram em reperfusão por duas horas. Em cada grupo, foram extraídas seis amostras de parênquima renal, com utilização de agulha tru-cut, para marcação com anticorpos anti-E-caderina e anti-ß-catenina por meio de imunoistoquímica. E-caderina e ß-catenina são diferencialmente expressas em segmentos do córtex e da medula em rim de cães e o uso da clorpromazina não alterou a expressão das duas proteínas.(AU)

Lesões do sistema urinário em 1.063 cães / Lesions of the urinary system in 1.063 dogs

Com o objetivo de realizar um estudo abrangente das lesões do sistema urinário em cães e determinar a sua prevalência, epidemiologia, importância clínica e possíveis causas associadas, foram revisados os protocolos de necropsias de cães realizadas no período de janeiro de 1999 a dezembro de 2010 no LPV-UFSM. Nesse período foram necropsiados 3.189 cães e destes, cerca de 30% apresentaram lesões no sistema urinário. Na maioria dos cães (79,1%) foram observadas lesões únicas e em aproximadamente 21% havia lesões múltiplas no sistema urinário, totalizando 1.373 lesões. Destas, 1.014 (73,8%) foram observadas no rim. No trato urinário inferior (TUI) foram diagnosticadas 359 (26,2%) lesões. Um terço das lesões no sistema urinário dos cães necropsiados foram causa de morte espontânea ou razão para eutanásia (ME/EUT). As demais foram consideradas como achados incidentais. As principais lesões renais diagnosticadas, em ordem decrescente de prevalência, foram: nefrite túbulo-intersticial, infarto, nefrite granulomatosa (parasitária), glomerulonefrite, neoplasmas metastáticos/multicêntricos, pielonefrite/ pielite e hidronefrose. As principais lesões do TUI diagnosticadas, em ordem decrescente de prevalência, foram: cistite, presença de inclusões virais (morbilivírus), urolitíase, dilatação da bexiga, ruptura de bexiga (com uroperitônio) e neoplasmas metastáticos/multicêntricos. As características epidemiológicas como sexo, raça e idade dos cães afetados tiveram variações expressivas de acordo com o tipo de lesão diagnosticada. Uremia foi observada em um número significativo de casos de ME/EUT e foi principalmente secundária a lesões renais.

The aim of this study was to determine the prevalence, epidemiology, clinical significance, and possible associated causes of the urinary system lesions in dogs necropsied between January 1999 and December 2010 at the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (LPV-UFSM). To accomplish this, the necropsy reports were analyzed retrospectively. In this time frame, 3,189 dogs were necropsied and about 30% had lesions in the urinary system. In most of the dogs (79.1%), lesions were single and in about 21% they were multiple, totalizing 1,373 lesions. Out of them, 1,014 (73.8%) were observed in the kidney and 359 (26.2%) were in the lower urinary tract (LUT). One third of the lesions in the urinary system were causes of spontaneous death or reason for euthanasia (SD/EUTH) of the affected dogs. The other two third of the lesions were considered incidental findings. The main renal lesions diagnosed, in descending order of prevalence, were: tubulointerstitial nephritis, infarct, granulomatous nephritis (parasitary), glomerulonephritis, metastatic/multicentric neoplasms, pyelonephritis/pyelitis, and hydronephrosis. The main LUT lesions, in descending order of prevalence, were: cystitis, presence of viral inclusions bodies (morbillivirus), urolithiasis, urinary bladder dilatation, urinary bladder rupture (with uroperitoneum), and metastatic/multicentric neoplasms. Epidemiological aspects such as gender, breed, and age of affected dogs had expressive variations according to the type of lesion diagnosed. Uremia was observed in a significant number of cases of SD/EUTH and was mostly due to renal lesions.

Heat-related injury in lambs.

The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable.

Photosensitisation, crystal-associated cholangiohepatopathy, and acute renal tubular necrosis in calves following ingestion of Phytolacca octandra (inkweed).

CASE HISTORY: In March 2006, an outbreak of photosensitivity affecting 6-8-month-old Friesian heifer calves on a farm in the Rangitikei district of New Zealand was investigated. The calves were grazing wheat stubble paddocks that also had a variety of weeds, especially Phytolacca octandra (inkweed). They also had access to pond water that contained potentially toxic concentrations of the cyanobacteria (blue-green algae) Microcystis and Planktothrix spp. CLINICAL FINDINGS: Initially, affected animals showed acute irritation, agitation, reluctance to walk, recumbency in some animals, hyperaemia of unpigmented skin and jaundice. Serum chemistry revealed elevated liver enzyme activities and azotaemia. Later in the outbreak, exudative dermatitis with formation of crusts on unpigmented skin, dehydration and inappetence were notable signs, as well as occasional diarrhoea. PATHOLOGICAL AND TOXICOLOGICAL FINDINGS: Post-mortem examinations following euthanasia of four severely affected calves and a fifth animal that died naturally revealed livers that were grossly orange brown and mildly enlarged, and kidneys that were enlarged and pale brown. Microscopic lesions in the liver were mild; however, small birefringent crystals in the bile ducts were noted in the first two cases. In contrast, renal lesions were moderate to severe, and included prominent segmental tubular necrosis, granular and cellular casts, and mild interstitial non-suppurative inflammation. In the kidneys of animals examined later in the outbreak, there was early interstitial fibrosis as well as tubular regeneration, with numerous hyaline casts in the renal medulla. Inkweed plants had been heavily browsed, and recognisable portions of the plant were found in the gastrointestinal tracts of affected calves. Chemical analysis of inkweed material revealed triterpene saponins. No known hepatotoxic or nephrotoxic plants were identified in the paddocks. The hepatic lesions were not consistent with published descriptions of cyanobacterial toxicity. Sporidesmin toxicity was ruled out. DIAGNOSIS: Hepatogenous photosensitivity, crystal-associated cholangiohepatopathy, toxic acute renal tubular necrosis, associated with the ingestion of P. octandra, and possibly complicated by cyanobacteria in the water. CLINICAL RELEVANCE: Crystal-associated cholangiohepatopathy with photosensitivity in cattle is rare, and has only been reported in steroidal saponin-containing Brachiaria decumbens poisoning, in Brazil. The consistent pattern of toxic acute renal tubular necrosis was similar to that caused by the ingestion of Quercus, Amaranthus or Lantana spp. A combination of toxicities was conceivable but circumstantial evidence strongly implicated P. octandra. Further toxicological investigation of this plant is warranted before it can be listed as a known nephrotoxin of cattle.

Renal tubular necrosis and interstitial hemorrhage ("turkey-egg kidney") in a circovirus-infected Yorkshire cross pig.

A juvenile Yorkshire cross pig with rapidly progressive acute renal failure was submitted for necropsy. There was marked edema and disseminated petechiation of both kidneys, producing the "turkey-egg" appearance that is characteristic of exotic diseases such as African and classical swine fever. Microscopic findings included renal tubular epithelial necrosis with extensive interstitial edema and hemorrhage; lymphoplasmacytic, eosinophilic, and histiocytic tubulointerstitial nephritis; and numerous botryoid intracytoplasmic inclusions within the renal tubular epithelium and interstitial macrophages. Porcine circovirus 2 (PCV2) was readily identified within these lesions by both PCV2-specific immunohistochemistical staining and electron microscopy. Tests for African and classical swine fever viruses, as well as bacterial cultures, were negative. The striking renal lesions in this pig were attributed to PCV2 infection and are distinct from those that are typical of other PCV2-associated diseases.

Ivermectin toxicosis after topical administration in dog-faced fruit bats (Cynopterus brachyotis).

Forty dog-faced fruit bats (Cynopterus brachyotis) were administered 1 drop of 1% ivermectin topically as part of a routine physical exam and deworming program, and 11 developed sudden generalized paresis. Six of the bats recovered within 24-48 hr, and the remaining 5 were presented recumbent and weak to the University of Florida Veterinary Medical Teaching Hospital. Ivermectin toxicosis was suspected, and the admitted bats died or were euthanatized within 3-5 days of the development of clinical signs despite supportive care. Three of the dead bats had renal tubular necrosis.

[A South American tapir (Tapirus terrestris) with peritonitis]. / Een zuid-amerikaanse tapir (Tapirus terrestris) met een peritonitis.

A 6-year-old male tapir was admitted because it had been anorexic for 1 day. On admission, the tapir weighed 160 kg. Its rectal temperature was 32.4 degrees C, its heart rate was 120 beats per minute, and its respiratory rate was 12 breaths per minute. The elasticity of the skin was diminished. Haematological evaluation upon admission revealed a haematocrit of 0.63 L.L-1., 6.0 G.L-1 leucocytes with 40 per cent band neutrophils. The concentrations of urea nitrogen and creatinine in plasma were raised (18.9 mmol L-1. and 475 mumol L-1., respectively). Severe combined acidosis was apparent; the venous pH was 6.965, the bicarbonate concentration was 13.7 mmol.L-1., and the venous pCO2 was 8.6 kPa. No strongyle eggs were isolated from faeces by flotation, but a faecal sample yielded a positive culture for Pseudomonas aeruginosa. Urinalysis revealed proteinuria and the presence of leucocytes and renal epithelial cells. Treatment with fluids, TMP/S (17.5 and 3.5 mg/kg body weight, twice a day, respectively), and clenbuterol (0.56 microgram/kg body weight, twice a day) intravenously was unsuccessful and the tapir died 4 days after hospitalization. At necropsy, peritonitis due to a colon infarct as well as chronic bronchopneumonia and renal tubulonecrosis were found. The antibiotic susceptibility of the bacteria isolated (Streptoc. sp., E. coli, and K. pneumoniae) from the tapir post-mortem was assessed.

Equine intestinal clostridiosis in a group of polo ponies in Dubai, U.A.E.

An acute outbreak of a C. perfringens Type C enterotoxemia in a polo club killed 8 polo ponies in less than 24 hours. Hay with a massive fungal contamination (Aspergillus and Fusarium sp.) is suspected to have triggered the enterotoxemia. Our cases show numerous similarities with the previously reported cases of EIC. However, acute toxic tubulonephrosis in the necropsied horses and longstanding elevation of AST and gamma GT-levels in survivors is unique in our cases.

Bog asphodel (Narthecium ossifragum) poisoning in cattle.

Fifteen cows among a herd of 50 suckler cows and calves rapidly lost body condition and became dull and anorexic after grazing pasture containing bog asphodel (Narthecium ossifragum) during the summer of 1989. The affected cows had evidence of kidney damage characterised by elevated plasma urea and creatinine concentrations. Eleven cows died and diffuse renal tubular necrosis was present in three cows which were examined post mortem. Similar renal lesions were reproduced experimentally by feeding bog asphodel to a healthy calf.

Acute oxalate poisoning attributable to ingestion of curly dock (Rumex crispus) in sheep.

Ten of 100 mature ewes were afflicted with acute oxalate toxicosis within 40 hours after being temporarily penned in a lot that contained considerable growing Rumex crispus (curly dock). Clinical signs of toxicosis included excess salivation, tremors, ataxia, and recumbency. Affected ewes were markedly hypocalcemic and azotemic. Oxalate crystals were not observed in urine. Gross postmortem lesions were minimal and nondiagnostic in 2 ewes that died peracutely, but perirenal edema and renal tubular degeneration were clearly observable in ewes euthanatized on the third day of toxicosis. Diagnosis of oxalate toxicosis was confirmed by histopathologic findings. Samples of Rumex spp contained 6.6 to 11.1% oxalic acid on a dry-weight basis, a concentration comparable with that in other oxalate-containing plants that have caused acute oxalate toxicosis.

Urinary indices of renal function in sheep with induced aminoglycoside nephrotoxicosis.

Aminoglycoside nephrotoxicosis (AGNT) was induced in ewes by daily SC administration of gentamicin. Changes in urinary indices of renal function during the development of AGNT are reported. Measurements from timed, volume-measured urine samples were made on days 0, 7, and 8 and included creatinine clearance, total excretion (TE) rates of electrolytes (Na, K, Cl, P) and urine volume. Measurements from free-catch urine samples (without volume measurement) were made daily and included fractional excretion (FE) rate of electrolytes, urine osmolality, and urine-to-serum osmolality and urine-to-serum creatinine ratios. With the onset of AGNT, FE rates of Na, K, Cl, and P- increased many fold above baseline values (200x, 4 to 5x, 6 to 9x, and 70 to 95x, respectively, on days 7 and 8), indicating decreased tubular reabsorption or increased tubular secretion. The increased FE rates were not representative of increases in total electrolyte excretion rates. The total excretion of Na (TENa) was mildly increased, TEK was decreased, TECl was unchanged, and TEP was significantly increased on days 7 and 8. Abnormal urinalysis results, glucosuria, and increased FEP preceded appreciable increase in serum creatinine concentration. Other abnormal urinary indices of renal function coincided with or followed the increase in serum creatinine concentration. Urinary indices may help characterize renal function associated with the disease state, but did not provide early indication of AGNT.

Canine chronic renal disease: prevalence and types of glomerulonephritis in the dog.

In a prospective survey, one hundred and eleven dogs with canine chronic renal disease, presenting to 24 veterinary practices in East Anglia and the West Midlands (geographical area 8,600 square miles) were identified. More than 20 different breeds were represented. In 76 cases, clinical details, blood and urine biochemistry, serology and kidney tissue for light and electron microscopy, and immunohistochemistry were obtained. Forty (52%) had glomerular (GN) and 36 (48%) non-glomerular (NGN) disease. Types of GN identified were (W.H.O. classification, number of cases in brackets): focal glomerulonephritis (gn) (5), diffuse mesangial proliferative gn (8), diffuse endocapillary proliferative gn (2), mesangiocapillary gn type I (8), diffuse crescentic gn (1), diffuse sclerosing gn (7), amyloid (6), unclassifiable gn (3). Eight dogs with GN and 13 with NGN had extra-renal lesions. In only one GN case (bacterial endocarditis) was the etiology clear. Proteinuria, but not age, breed, sex, serum creatinine or hematuria, discriminated between GN and NGN groups. This prospective survey identifies GN, with morphological types as found in humans, as a common cause of canine chronic renal disease.

Narthecium asiaticum Maxim. Poisoning of grazing cattle: observations on spontaneous and experimental cases.

A total of 39 Holstein cattle were grazed in tracts of wild grassland on account of shortage in pasture grass. Twenty-nine cattle were affected and 26 of them died during a 21-day period. The main signs were depression, anorexia, ascites, and oliguria. There was elevated serum urea nitrogen and sugar and protein in the urine. Pathological examination revealed turbid swelling of the kidney, an increase in the amount of fluid in the body cavity, edema in the perirenal adipose tissue and hemorrhage in various visceral organs and tissues. Histologically, acute tubular necrosis in the kidney, hypoplasia of the erythroblast series in the bone marrow, atrophy and degeneration of the lymphatic tissue and focal necrosis of the liver were observed in many of the cattle. Among cows experimentally fed Narthecium asiaticum Maxim., Polygonum sachalinense Fr. Schum., and Vitis coignetiae Pulliat which were presumed to have been ingested in large amounts by grazing cattle in the field, the cows fed N. asiaticum revealed the clinical, biochemical and pathological changes similar to those noticed in naturally affected cattle. Cows fed P. sachalinense and V. coignetiae showed no distinct systemic symptoms except transient anorexia and hypothermia.