Mesenchymal stem cell transplantation: Systematic review, meta-analysis and clinical applications for acute kidney injury and chronic kidney disease in dogs and cats.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy requires different therapeutic goals. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects. This work reports the results of a meta-analysis about the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed PRISMA guidelines. Data were screened, selected, and extracted with characteristics about the studies. The kinds of injury were classified according to their identification and the risk of bias was calculated by the system SYRCLE. The results of each group were combined by the inverse variance method. The heterogeneity was evaluated by the I2 test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of applications and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. At all, 4742 articles were found. Of these, 40 were selected for eligibility, 16 underwent qualitative analysis and 9 to the quantitative. The results denote advantage to the group treated with MSC over placebo. A statistical difference was observed both in combined analysis and in the subgroups division. However, a high heterogeneity was found, which indicates considerable variation between the studies, which indicates caution in generalize the results.

B-mode and Doppler ultrasound of bitches' kidneys with mammary neoplasia submitted to adjuvant chemotherapy / Ultrassonografia modo-B e Doppler dos rins de cadelas com neoplasias mamárias submetidas à quimioterapia adjuvante

Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

As neoplasias mamárias representam o tipo de neoplasma mais frequentemente diagnosticado em fêmeas da espécie canina. Embora a remoção cirúrgica seja o procedimento de eleição para a conduta terapêutica, os protocolos quimioterápicos aparecem como importantes aliados e adjuvantes. Apesar dos grandes avanços ocorridos na área da terapia oncológica, as repercussões sistêmicas destes fármacos ainda impõem importantes limitações ao seu uso. Neste sentido, o desenvolvimento de protocolos terapêuticos cada vez mais direcionados e o monitoramento preventivo dos pacientes representam estratégias importantes para evitar possíveis complicações - dentre elas, a injúria renal aguda (IRA). Rotineiramente, a avaliação ultrassonográfica é utilizada para identificação de variações morfológicas ou metastáticas em órgãos da cavidade abdominal. Atuando de forma complementar à avaliação em modo-B, o mapeamento Doppler mostra-se eficiente no reconhecimento de alterações na hemodinâmica vascular. Portanto, o objetivo do presente estudo foi avaliar a utilização da ultrassonografia modo-B e Doppler como método para identificação de alterações morfológicas e hemodinâmicas renais em cadelas com neoplasias mamárias submetidas a protocolos quimioterápicos adjuvantes que associam a gencitabina à carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto a raça e com idades entre sete e 13 anos. Os animais foram avaliados ultrassonograficamente em dois momentos distintos durante três ciclos quimioterápicos consecutivos: antes (T0) e uma hora e meia após a realização de cada ciclo (T1), totalizando 42 dias. Não foram observadas alterações morfológicas em modo-B ao longo do protocolo quimioterápico. Entretanto, os índices dopplervelocimétricos demonstraram diferenças estatísticas antes (T0) e após (T1) a administração dos fármacos. Concluiu-se que a ultrassonografia Doppler pode ser utilizada como método complementar para o monitoramento da resposta renal de pacientes expostos a fármacos nefrotóxicos e potencialmente causadores de injúrias renais.

Evaluation of kidney injury through early markers in canine pyometra / Avaliação de lesão renal através de marcadores precoce em piometra canina

Fourteen female dogs diagnosed with pyometra were studied at three separate times: at diagnosis (T0) and 24 h (T1) and 10-15 days (T2) after ovariohysterectomy (OH). The means of the markers, symmetric dimethylarginine (SDMA) (17.71 to 26.54 µg/dL) and the urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) (1.06 to 2.62 U/mg), varied, showing an increase with time. Further, the elevation of gamma-glutamyl transferase (uGGT) (56.61 to 128.12 U/L) and the urinary protein to creatinine ratio (RPC) (0.26 to 1.24) was evident at T0 and T1. A reduction in the means of RPC, uGGT, and uGGT/uCr was observed 10-15 days after OH. Despite the elevation of these markers, the concentration of creatinine (1.11 to 1.40 mg/dL), urea (40.07 to 67.16 mg/dL), and urinary specific gravity (1.027 to 1.028) only presented slight variation. In canine pyometra, complications secondary to acute renal injury may be present that may be mild and transient in most treated animals. As elevation in SDMA and RPC preceded changes in creatinine levels for the evaluation of glomerular filtration, tubular markers could assist in the early identification of renal damage in canine pyometra.(AU)

Catorze cadelas com diagnóstico de piometra foram estudadas em três tempos distintos, sendo no momento do diagnóstico (T0), 24 horas (T1) e 10 a 15 dias (T2) após a ovário-histerectomia (OH). O objetivo foi avaliar o uso de diferentes biomarcadores renais em cadelas com piometra e estimar suas precocidades diante do agravo. As médias em dimetilarginina simétrica (SDMA) (17,71 a 26,54µg/dL) e relação gama-glutamil transferase e creatinina urinária (uGGT/uCr) (1,06 a 2,62U/mg) variara, apresentando aumento em todos os momentos. Já a elevação do gama-glutamil transferase (uGGT) (56,61 a 128,12 U/L) e da razão proteína e creatinina urinárias (RPC) (0,26 a 1,24) foram evidenciadas nos dois primeiros tempos. Uma redução na média do RPC, uGGT e uGGT/uCr foi observada 10-15 dias após a implantação do tratamento (OH). Apesar da elevação desses marcadores, a concentração de creatinina (1,11 a 1,40mg/dL), ureia (40,07 a 67,16mg/dL) e densidade urinária (1,027 a 1,028) sofreram poucas variações. Em piometra canina, as complicações renais agudas secundárias podem estar presentes, ainda que leve e transitória nos animais tratados. Os marcadores tubulares foram considerados precoces na injúria renal aguda. Além disso, a SDMA e o RPC antecederam as alterações de creatinina em todos os tempos analisados.(AU)

Kidney injury molecule-1 and urinary gamma-glutamyl transferase as biomarkers of acute kidney injury in cats.

OBJECTIVES: To evaluate the concentration of kidney injury molecule-1 and activity of urinary gamma-glutamyl transferase in cats with urethral obstruction and healthy cats. MATERIALS AND METHODS: Blood and urine samples were collected from a group of 15 healthy cats (control group) and a group of 20 cats with urethral obstruction at presentation, and 24 hours and 7 days after unblocking the obstruction. The serum creatinine, urinary creatinine and urinary gamma-glutamyl transferase were measured by spectrophotometry and kidney injury molecule-1 by the sandwich enzyme-linked immunosorbent assay. RESULTS: On presentation, cats with obstruction had serum creatinine concentration and urinary gamma-glutamyl transferase index higher than healthy cats (mean difference 544 µmol/L, 95% confidence intervals 222 to 865 µmol/L, and 0.0022 U/µmol-uCre, 0.00043 to 0.0039 U/µmol-uCre, respectively), urine creatinine concentration lower (mean difference 25,624 µmol/L, 17,329 to 33,919 µmol/L), and no significant difference in the kidney injury molecule-1/urinary creatinine ratio (mean difference 13 pg/µmol-uCre, -33 to 59 pg/µmol-uCre). In the group of cats with urinary obstruction, over time serum creatinine decreased, urine creatinine increased, urinary gamma-glutamyl transferase index did not change significantly, and kidney injury molecule-1/urinary creatinine ratio increased. CLINICAL SIGNIFICANCE: Cats with post-renal obstruction and potential intrinsic renal damage had higher urinary gamma-glutamyl transferase index than healthy cats at the time of presentation and showed increase in kidney injury molecule-1/urinary creatinine ratio over time.

Correlation between renal ultrasonography and serum cystatin C in acute kidney disease of critically ill dogs / Correlação entre a ultrassonografia e a determinação da cistatina C sérica em cães admitidos em unidade de terapia

Acute kidney injury (AKI) is defined as the rapid decline in kidney function. Its development is related to critical clinical statuses, such as sepsis, complicated post-surgical recovery, and infectious diseases. Serum cystatin C (CysC) has the best correlation with the glomerular filtration rate. Ultrasonography stands out because it is highly accessible and can be done at the bedside. Twenty-eight dogs admitted to the intensive care unit with serum creatinine values <1.6 mg/dL and at-risk factors of AKI development were selected. CysC measurements and ultrasound assessments were performed daily for 72 hours. Using CysC dosage, 22/28 animals (78.6%) were considered to have AKI, and 17/22 had ultrasound compatible with AKI changes, demonstrating moderate agreement with CysC dosage. Increased cortical renal echogenicity is the most prevalent alteration in critically ill patients and is correlated with serum increases in CysC and is associated with renal structural damage.

A injúria renal aguda (IRA) é definida como o declínio rápido da função renal. Seu desenvolvimento está relacionado a quadros clínicos críticos, como sepse, pós-operatório complicado e doenças infecciosas. A cistatina C sérica (CisC) tem melhor correlação com taxa de filtração glomerular. A ultrassonografia se destaca por ser altamente acessível e pode ser realizada à beira do leito. Foram selecionados 28 cães, internados em unidade de terapia intensiva, com valores de creatinina sérica <1,6mg/dL e fatores de risco para o desenvolvimento de IRA. Medições de CisC e avaliações ultrassonográficas foram realizadas diariamente por 72 horas. Utilizando-se a dosagem de CisC, 22/28 animais (78,6%) foram considerados portadores de IRA e 17/22 apresentaram ultrassom compatível com alterações de IRA, demonstrando concordância moderada com a dosagem de CisC. O aumento da ecogenicidade cortical renal é a alteração mais prevalente em pacientes críticos, está correlacionado com aumentos séricos de CisC e associado a dano estrutural renal.

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.(AU)

Hipoplasia renal bilateral em felino / Bilateral renal hypoplasia in feline

A hipoplasia renal ocorre quando há o desenvolvimento incompleto do rim, resultando em um menor número de néfrons, lóbulos e cálices ao nascimento do animal. A gravidade dessa anomalia depende do nível de acometimento. Quando unilateral, ocorre a hipertrofia compensatória do rim saudável e, em casos bilaterais, é frequente a ocorrência de insuficiência renal e infecções. Foi retratada como uma afecção hereditária em algumas raças puras ou mestiças de suínos, potros, caprinos, bovinos e cães, contudo, é incomum em felinos. O presente trabalho tem como objetivo relatar o caso de uma felina, sem raça definida, de dois meses de idade, com queixa de apatia, anorexia e êmes por três dias. No exame físico, foi observada desidratação estimada em 10%, tempo de preenchimento capilar de três segundos, hipotermia, hipoglicemia e letargia. Frente a essas alterações, foram solicitados exames complementares para melhor elucidação do quadro. Os exames bioquímicos revelaram azotemia e hiperfosfatemia grave, bem como hipercalcemia e hipercalemia leve. Já a urinálise, indicou redução da densidade urinária associada à presença de cilindros hialinos e céreos. A ultrassonografia abdominal evidenciou perda de diferenciação córtico-medular e diminuição de ambos os rins, alterações essas compatíveis com nefropatia. Instituiu-se tratamento paliativo visando minimizar complicações secundárias da injúria renal aguda, contudo, a paciente veio a óbito. Na necropsia, os rins apresentavam tamanho reduzido bilateralmente e o exame histopatológico revelou a presença de moderados glomérulos primitivos multifocais associados à distensão do espaço glomerular. A avaliação clínica e as lesões histopatológicas foram consistentes com o diagnóstico de hipoplasia renal congênita.

Renal hypoplasia occurs when there is incomplete development of the kidney, resulting in fewer nephrons, lobes and calyces at birth. The severity of this anomaly depends on the level of involvement. When unilateral, compensatory hypertrophy of the healthy kidney occurs and, in bilateral cases, renal failure and infections are frequent. It has been portrayed as an inherited condition in some pure or mixed breeds of pigs, foals, goats, cattle and dogs, however, it is uncommon in felines. This paper aims to report the case of a feline, mixed breed, two months old, with complaints of apathy, anorexia and emesis for three days. Physical examination showed an estimated dehydration of 10%, capillary refilling time of three seconds, hypothermia, hypoglycemia and lethargy. In view of these changes, complementary exams were requested to better clarify the condition. Biochemical examinations revealed severe azotemia and hyperphosphatemia, as well as hypercalcemia and mild hyperkalemia. Urinalysis, on the other hand, indicated a reduction in urinary density associated with the presence of hyaline and brain cylinders. Abdominal ultrasound showed a loss of corticomedullary differentiation and a decrease in both kidneys, changes compatible with nephropathy. Palliative treatment was instituted in order to minimize secondary complications of acute kidney injury, however, the patient died. At necropsy, the kidneys were bilaterally reduced in size and histopathological examination revealed the presence of moderate multifocal primitive glomeruli associated with distention of the glomerular space. Clinical evaluation and histopathological lesions were consistent with the diagnosis of congenital renal hypoplasia.

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Inflammatory processes are believed to play an important role in immune response to maintain tissue homeostasis by activating cellular signaling pathways and releasing inflammatory mediators in the injured tissue. Although acute inflammation can be considered protective, an uncontrolled inflammation may evolve to tissue damage, leading to chronic inflammatory diseases. Inflammation can be considered the major factor involved in the pathological progression of acute and chronic kidney diseases. Functional characteristics of this organ increase its vulnerability to developing various forms of injuries, including acute kidney injury (AKI) and chronic kidney disease (CKD). In view of translational research, several discoveries should be considered regarding the pathogenesis of the inflammatory process, which results in the validation of biomarkers for early detection of kidney diseases. Biomarkers enable the identification of proinflammatory mediators in kidney affections, based on laboratory research applied to clinical practice. Some inflammatory molecules can be useful biomarkers for the detection and diagnosis of kidney diseases, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin 18.(AU)

Clinical and ultrasound variables for early diagnosis of septic acute kidney injury in bitches with pyometra.

The aetiology of septic acute kidney injury (AKI) is not completely elucidated. Early identification of AKI in septic patients is considered to improve survival rate since it allows rapid treatment onset. We evaluated clinical, haematological, urinary, B-mode, spectral Doppler, and contrast-enhanced ultrasound variables in 20 bitches with pyometra as sepsis models and 12 healthy controls. All animals with pyometra presented some degree of renal damage on histological examination; however, sequential organ failure assessment (SOFA) classified only 40% cases with sepsis. AKI derived from systemic infection was identified in 57% of cases with hypoperfusion and in 22% with inflammation, being an affection of multifactorial origin. Among the evaluated parameters, urinary protein/creatinine ratio >0.15, serum albumin <2.94 mg/dL, time-averaged minimum velocity <21.5 cm/s, renal length/aorta diameter ratio >5.93, pulsatility index >1.53, haematocrit <45%, time-averaged maximum velocity <45.7 cm/s, haemoglobin <16 g/dL, leukocytes >12.53 × 103/uL, and cortical contrast peak intensity <69%, in the order of accuracy, are significant indicators of septic AKI with an accuracy >80%. Thus, AKI is a very prevalent condition in septic patients, derived mainly from changes in renal perfusion and inflammation. Additionally, reviewing the SOFA score parameters is suggested to identify renal failure.

Effects of cyclosporine on ischemia-reperfusion injuries in rat kidneys. An experimental model

Abstract Purpose To assess Cyclosporine A (CsA) therapy at an intraperitoneal dose of 15 mg.kg -1 in a rodent model of non-septic renal ischemia. Methods Twenty male Wistar rats were randomized to receive CsA therapy or none therapy before undergoing 30 minutes of renal ischemia followed by reperfusion. Additionally, 10 rats were randomized to undergo the same surgical procedure of the aforementioned animals with neither ischemia nor CsA therapy. Twelve hours after kidney ischemia, the left kidneys were evaluated for histological injury according to Park's criteria. Serum creatinine (Cr), urea nitrogen (Ur) and sodium levels were obtained at different times of the experimental protocol. Results Rodents in the CsA group showed negative results (p<0.05) in serum variables (Cr: 0.41±0.05mg/dL vs . 4.17±1.25mg/dL; Ur: 40.90±3.98mg/dL vs . 187.70±22.93mg/dL) even the non CsA or control group (Cr: 0.35±0.07mg/dL vs . 3.80±1.20mg/dL; Ur: 40.10±4.70mg/dL vs . 184.50±49.80mg/dL). The negative results were also verified in histological evaluation, CsA group had 50% in the very severe grade of lesion, 10% in the severe and 40% in the moderate to severe whereas the control group had 90% in the very severe grade. Conclusion CsA was incapable of preventing the deleterious effects of ischemia-reperfusion injury in rat kidneys.(AU)

Fatal lancehead pit viper (Bothrops spp.) envenomation in horses.

Snake bite envenomations in farm animals are generally overestimated as the cause of mortality in rural areas in Latin America. However, most cases are based only on anecdotal information and assumptions, and lack diagnostic evidence. There are few proven reports of envenomation and death in horses caused by snakebites from members of the Bothrops genus (lancehead pit vipers). This study presents epidemiological and clinical-pathological findings of fatal bothropic envenomation in horses from Central Western Brazil in order to contribute to the correct diagnosis of this condition. A survey of the records of equine necropsies from the Veterinary Pathology Laboratories of the University of Brasilia, Federal University of Mato Grosso and Federal University of Mato Grosso do Sul, from January 2010 to February 2018, was performed. Five fatal cases of bothropic snakebite were identified in 755 necropsies of horses, corresponding to 0.66% of these cases, ranging annually from 0.33% to 0.89%. The main necropsy findings were marked swelling and diffuse subcutaneous hemorrhage, and identification of the fang marks in 2 out of five horses. Hemorrhage in most organs and tissues was the pathological hallmark of systemic envenomation. Myonecrosis, dermonecrosis, and moderate to severe kidney degeneration and necrosis were also observed. Fatal Bothrops snakebites in horses have a low occurrence in Central Western Brazil and most cases occur in the rainy season. The diagnosis of this condition may be substantiated by clinical signs and pathological findings. Local hemorrhage and necrosis, systemic hemorrhagic disorders and injuries related to acute kidney injury are the predominant clinical signs. These findings should be considered in the diagnosis and therapeutic management of these envenomations.

Retrospective evaluation of paired plasma creatinine and chloride concentrations following hetastarch administration in anesthetized dogs (2002-2015): 244 cases.

OBJECTIVE: To evaluate changes in serum creatinine and chloride concentrations in anesthetized dogs that received 6% hydroxyethyl starch (HES) 670/0.7. DESIGN: Retrospective case series, 2002-2015. SETTING: University veterinary teaching hospital. ANIMALS: Two hundred forty-four client-owned dogs undergoing general anesthesia that received an HES solution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs that received an HES solution (6%, 670/0.7) while under general anesthesia during the study period were reviewed. Information obtained from the medical record included patient signalment, reason for anesthesia or diagnosis, body weight, amount of HES solution administered, pre- and postanesthesia creatinine value, pre- and postanesthesia chloride value, and day interval between measurements. Corrected chloride values were used for all statistical analysis. Dogs received a median dose of 6.3 mL/kg hetastarch during anesthesia. Median preanesthesia creatinine and corrected chloride values were 79.5 µmol/L (0.9 mg/dL) (range 8.8-689.5 µmol/L [0.1-7.8 mg/dL]) and 111 mmol/L (111 mEq/L) (range 80-123 mmol/L [80-123 mg/dL]), respectively. Median postanesthesia creatinine was 57.4 µmol/L (0.65 mg/dL) (8.8-716 µmol/L [0.1-8.1 mg/dL]). Median postanesthesia corrected chloride was 115 mmol/L (115 mEq/L) (range 87.5-129.6 mmol/L [87.5-129.6 mEq/L]). Mann-Whitney test analysis revealed a significant decrease in creatinine (Δ Cr 17.7 µmol/L [0.2 mg/dL], P < 0.01) and a significant increase in corrected chloride (Δ Cl 4.1 mmol/L [4.1mEq/L], P < 0.01) between pre- and postanesthesia values. CONCLUSIONS: In a mixed population of hospitalized dogs undergoing general anesthesia that received a median dose of 6 mL/kg of HES, creatinine was lower and chloride was higher in the postanesthetic than in the preanesthetic period. The clinical significance of these changes and the role that HES administration played in them relative to concurrent therapies is unknown.

Milk fat globule-epidermal growth factor 8 (MFG-E8) attenuates sepsis-induced acute kidney injury by inhibiting NF-kappa B signaling pathway

Purpose:To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI).Methods:Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway.Results:MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-𝜅B signaling pathway in SAKI.Conclusion:MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.(AU)

Salvianolic acid A alleviates the renal damage in rats with chronic renal failure

Purpose:To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF).Methods:The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined.Results:After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05).Conclusion:SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.(AU)

Insuficiência renal aguda em equinos: revisão de literatura / Acute renal failure in horses: literatura review / Insuficiencia renal aguda em equinos: revisión de literatura

A insuficiência renal aguda (IRA) é caracterizada pela diminuição abrupta da taxa de filtração glomerular, aumento dos níveis séricos de ureia e creatinina e desequilíbrios hidroelétricos e ácido-básicos. Os equinos com maior probabilidade de desenvolverem IRA apresentam doenças que resultam em hipovolemia, endotoxemia ou pigmentúria (hemoglobinúria e mioglobinúria) e possuem histórico de terapias com medicamentos nefrotóxicos, especialmente anti-inflamatórios não esteroidais e aminoglicosídeos. As manifestações clínicas incluem oligúria nos estágios iniciais e poliúria na fase de recuperação, com o diagnóstico efetuado a partir de avaliação laboratorial e ultrassonografia. O tratamento precoce, através de fluidoterapia em associação a diuréticos, vasoativos e diálise permite o restabelecimento do fluxo sanguíneo renal, e quando realizado corretamente é capaz de reverter o quadro clínico do paciente. O prognóstico dependerá da duração da insuficiência renal, resposta à terapia instituída e desenvolvimentos de complicações. O objetivo desta revisão literária é prover ao médico-veterinário informações a respeito da patofisiologia, diagnóstico e tratamento da IRA nos equinos, com o intuito de se evitar erros nas condutas a serem tomadas diante dessa afecção e aumentar o êxito nas intervenções realizadas.

Acute renal failure (ARF) is characterized by an abrupt decrease in the rate of glomerular filtration, increased serum urea and creatinine levels, and hydroelectric and acid-base imbalances. Equines most likely to develop ARF include diseases resulting in hypovolemia, endotoxemia or pigmenturia (hemoglobinuria and myoglobinuria) and have a history of therapies with nephrotoxic drugs, especially nonsteroidal anti-inflammatory drugs and aminoglycosides. Clinical manifestations include oliguria in the early stages and polyuria in the recovery phase, with diagnosis made from laboratory and ultrasonography. Early treatment through fluid therapy in combination with diuretics, vasoactive and dialysis allows the reestablishment of renal blood flow, and when performed correctly is able to reverse the clinical picture of the patient. The prognosis will depend on the duration of renal failure, response to therapy instituted and developments of complications. The objective of this literature review is to provide the veterinarian with information regarding the pathophysiology, diagnosis and treatment of ARF in horses, in order to avoid errors in the behaviors to be taken in the face of this affection and to increase the success in the interventions carried out.

La insuficiencia renal aguda (IRA) se caracteriza por la disminución abrupta de la tasa de filtración glomerular, aumento de los niveles séricos de urea y creatinina y desequilibrios hidroeléctricos y ácido-básicos. Los equinos con mayor probabilidad de desarrollar IRA presentan enfermedades que resultan en hipovolemia, endotoxemia o hemorragia (hemoglobinuria y mioglobinuria) y poseen antecedentes de terapias con medicamentos nefrotóxicos, especialmente antiinflamatorios no esteroidales y aminoglucósidos. Las manifestaciones clínicas incluyen oliguria en las etapas iniciales y poliuria en la fase de recuperación, con el diagnóstico efectuado a partir de evaluación de laboratorio y ultrassonografia. El tratamiento precoz, a través de fluidoterapia en combinación con diuréticos, vasoactivos y diálisis permite el restablecimiento del flujo sanguíneo renal, y cuando se realiza correctamente es capaz de revertir el cuadro clínico del paciente. El pronóstico dependerá de la duración de la insuficiencia renal, respuesta a la terapia instituida y desarrollos de complicaciones. El objetivo de esta revisión literaria es proveer al médico-veterinario informaciones acerca de la patofisiología, diagnóstico y tratamiento de la IRA en los equinos, con el propósito de evitar errores en las conductas a ser tomadas ante esta afección y aumentar el éxito en las intervenciones realizadas.

Insuficiência renal aguda em equinos: revisão de literatura / Acute renal failure in horses: literatura review / Insuficiencia renal aguda em equinos: revisión de literatura

A insuficiência renal aguda (IRA) é caracterizada pela diminuição abrupta da taxa de filtração glomerular, aumento dos níveis séricos de ureia e creatinina e desequilíbrios hidroelétricos e ácido-básicos. Os equinos com maior probabilidade de desenvolverem IRA apresentam doenças que resultam em hipovolemia, endotoxemia ou pigmentúria (hemoglobinúria e mioglobinúria) e possuem histórico de terapias com medicamentos nefrotóxicos, especialmente anti-inflamatórios não esteroidais e aminoglicosídeos. As manifestações clínicas incluem oligúria nos estágios iniciais e poliúria na fase de recuperação, com o diagnóstico efetuado a partir de avaliação laboratorial e ultrassonografia. O tratamento precoce, através de fluidoterapia em associação a diuréticos, vasoativos e diálise permite o restabelecimento do fluxo sanguíneo renal, e quando realizado corretamente é capaz de reverter o quadro clínico do paciente. O prognóstico dependerá da duração da insuficiência renal, resposta à terapia instituída e desenvolvimentos de complicações. O objetivo desta revisão literária é prover ao médico-veterinário informações a respeito da patofisiologia, diagnóstico e tratamento da IRA nos equinos, com o intuito de se evitar erros nas condutas a serem tomadas diante dessa afecção e aumentar o êxito nas intervenções realizadas.(AU)

Acute renal failure (ARF) is characterized by an abrupt decrease in the rate of glomerular filtration, increased serum urea and creatinine levels, and hydroelectric and acid-base imbalances. Equines most likely to develop ARF include diseases resulting in hypovolemia, endotoxemia or pigmenturia (hemoglobinuria and myoglobinuria) and have a history of therapies with nephrotoxic drugs, especially nonsteroidal anti-inflammatory drugs and aminoglycosides. Clinical manifestations include oliguria in the early stages and polyuria in the recovery phase, with diagnosis made from laboratory and ultrasonography. Early treatment through fluid therapy in combination with diuretics, vasoactive and dialysis allows the reestablishment of renal blood flow, and when performed correctly is able to reverse the clinical picture of the patient. The prognosis will depend on the duration of renal failure, response to therapy instituted and developments of complications. The objective of this literature review is to provide the veterinarian with information regarding the pathophysiology, diagnosis and treatment of ARF in horses, in order to avoid errors in the behaviors to be taken in the face of this affection and to increase the success in the interventions carried out.(AU)

La insuficiencia renal aguda (IRA) se caracteriza por la disminución abrupta de la tasa de filtración glomerular, aumento de los niveles séricos de urea y creatinina y desequilibrios hidroeléctricos y ácido-básicos. Los equinos con mayor probabilidad de desarrollar IRA presentan enfermedades que resultan en hipovolemia, endotoxemia o hemorragia (hemoglobinuria y mioglobinuria) y poseen antecedentes de terapias con medicamentos nefrotóxicos, especialmente antiinflamatorios no esteroidales y aminoglucósidos. Las manifestaciones clínicas incluyen oliguria en las etapas iniciales y poliuria en la fase de recuperación, con el diagnóstico efectuado a partir de evaluación de laboratorio y ultrassonografia. El tratamiento precoz, a través de fluidoterapia en combinación con diuréticos, vasoactivos y diálisis permite el restablecimiento del flujo sanguíneo renal, y cuando se realiza correctamente es capaz de revertir el cuadro clínico del paciente. El pronóstico dependerá de la duración de la insuficiencia renal, respuesta a la terapia instituida y desarrollos de complicaciones. El objetivo de esta revisión literaria es proveer al médico-veterinario informaciones acerca de la patofisiología, diagnóstico y tratamiento de la IRA en los equinos, con el propósito de evitar errores en las conductas a ser tomadas ante esta afección y aumentar el éxito en las intervenciones realizadas.(AU)

Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window

Purpose:To evaluate renal repair in rats who had renal infarction induced by the obstruction of blood flow in the renal artery and were treated with transplantation of adipose tissue derived mesenchymal stem cellMethods:16-week-old Wistar rats (n=72) were used, submitted to celiotomy and had of the renal artery and vein clipped for 24 hours. The animals were randomly assigned to 10 experimental homogeneous groups, corresponding to the treatments with phosphate-buffered saline (PBS) or adipose tissue derived mesenchymal stem cell (ADSC), duration of application (24 or 48 hours), and site of transplantation (lateral vein of the tail or intrarenal). After the treatments were performed, at 8 and 31 days, four animals in each group were subjected to left nephrectomy for histological studies.Results:Histologically, a higher amount of cell debris and tubules devoid of the epithelium and a higher degree of necrosis were observed in the groups treated with PBS, as opposed to a low degree of necrosis and higher tubular vascularization in the groups treated with ADSC, particularly in the group treated with intrarenal ADSC 48 hours after injury.Conclusion:The transplantation of ADSC positively contributed to the replacement of necrotic tissue by renal tubular cells, vascularization of the renal parenchyma, and restoration of the organ function.(AU)

Cistatina C sérica em cães criticamente enfermos em UTI / Cystatin C in critically ill dogs at UTI

A lesão renal aguda (IRA) é uma síndrome complexa, associada à progressão desfavorável, especialmente em cães na unidade de terapia intensiva (UTI) e apresenta alta morbidade e mortalidade. O diagnóstico de IRA requer combinação de testes laboratoriais, como a creatinina sérica e ureia, considerados pouco sensíveis e específicos para a detecção precoce de graus discretos durante a perda de função renal. O biomarcador cistatina C é considerado superior por apresentar uma melhor correlação com a taxa de filtração glomerular. No entanto, existem poucos estudos que demonstram a utilidade da cistatina C em cães na UTI. O objetivo deste estudo foi comparar a cistatina C com o nível sérico de creatinina para detectar o estágio inicial da IRA em cães em terapia intensiva. As dosagens desses analitos foram realizadas no momento da admissão, 24 e 48 horas após. A cistatina C apresentou concentrações mais elevadas em 78,6%, enquanto a creatinina sérica aumentou apenas em 28,5% dos cães. Os resultados demonstraram que a cistatina C pode ser utilizada para a detecção precoce de lesão renal aguda em cães de UTIs devido à sua maior sensibilidade em relação aos marcadores tradicionais.(AU)

Acute kidney injury (AKI) is a complex syndrome, associated with unfavorable progression, especially in dogs in the intensive care unit (ICU), and presents high morbidity and mortality. The diagnosis of AKI requires a combination of laboratory tests, such as serum creatinine and urea, considered to be poorly sensitive and specific for the early detection of discrete degrees during loss of renal function. The biomarker cystatin C is considered superior because it has a better correlation with the glomerular filtration rate. However, there are few studies that demonstrate the utility of cystatin C in dogs in ICU. The objective of this study was to compare cystatin C to creatinine serum level to detect early stage of AKI in dogs in an intensive care. Measurements of these analytes were performed at the time of admission, 24 and 48 hours after. Serum cystatin C presented higher concentrations in 78.6% while serum creatinina elevated in only 28.5% of the dogs. The results demonstrated that cystatin C can be used for the early detection of acute kidney injury in dogs in ICUs because of its greater sensitivity compared to traditional markers.(AU)

Cistatina C sérica em cães criticamente enfermos em UTI / Cystatin C in critically ill dogs at UTI

A lesão renal aguda (IRA) é uma síndrome complexa, associada à progressão desfavorável, especialmente em cães na unidade de terapia intensiva (UTI) e apresenta alta morbidade e mortalidade. O diagnóstico de IRA requer combinação de testes laboratoriais, como a creatinina sérica e ureia, considerados pouco sensíveis e específicos para a detecção precoce de graus discretos durante a perda de função renal. O biomarcador cistatina C é considerado superior por apresentar uma melhor correlação com a taxa de filtração glomerular. No entanto, existem poucos estudos que demonstram a utilidade da cistatina C em cães na UTI. O objetivo deste estudo foi comparar a cistatina C com o nível sérico de creatinina para detectar o estágio inicial da IRA em cães em terapia intensiva. As dosagens desses analitos foram realizadas no momento da admissão, 24 e 48 horas após. A cistatina C apresentou concentrações mais elevadas em 78,6%, enquanto a creatinina sérica aumentou apenas em 28,5% dos cães. Os resultados demonstraram que a cistatina C pode ser utilizada para a detecção precoce de lesão renal aguda em cães de UTIs devido à sua maior sensibilidade em relação aos marcadores tradicionais.(AU)

Acute kidney injury (AKI) is a complex syndrome, associated with unfavorable progression, especially in dogs in the intensive care unit (ICU), and presents high morbidity and mortality. The diagnosis of AKI requires a combination of laboratory tests, such as serum creatinine and urea, considered to be poorly sensitive and specific for the early detection of discrete degrees during loss of renal function. The biomarker cystatin C is considered superior because it has a better correlation with the glomerular filtration rate. However, there are few studies that demonstrate the utility of cystatin C in dogs in ICU. The objective of this study was to compare cystatin C to creatinine serum level to detect early stage of AKI in dogs in an intensive care. Measurements of these analytes were performed at the time of admission, 24 and 48 hours after. Serum cystatin C presented higher concentrations in 78.6% while serum creatinina elevated in only 28.5% of the dogs. The results demonstrated that cystatin C can be used for the early detection of acute kidney injury in dogs in ICUs because of its greater sensitivity compared to traditional markers.(AU)

Acute kidney injury in cats and dogs: A proportional meta-analysis of case series studies.

INTRODUCTION: Risk of mortality in the setting of acute kidney injury (AKI) in cats and dogs remains unclear. OBJECTIVES: To evaluate the incidence of mortality in cats and dogs with AKI based on etiology (i.e. infectious versus non-infectious; receiving dialysis versus conservative treatment). MATERIALS AND METHODS: Ovid Medline, EMBASE, and LILACS were searched up to July 2016. Articles were deemed eligible if they were case series studies evaluating the incidence of all-cause mortality in cats and dogs with AKI, regardless of etiology or the nature of treatment. RESULTS: Eighteen case series involving 1,201animalsproved eligible. The pooled proportions for overall mortality were: cats53.1% [95% CI 0.475, 0.586; I2 = 11,9%, p = 0.3352]; dogs 45.0% [95% CI 0.33, 0.58; I2 = 91.5%, P < 0.0001]. A non-significant increase in overall mortality risk was found among dialysed animals relative to those managed with conservative treatment, independent of animal type and the etiology of their AKI. The pooled proportions for overall mortality according to etiology, regardless of treatment type, were: AKI due infectious etiology for cats and dogs, 19.2% [95% CI 0.134, 0.258; I2 = 37.7%, P = 0.0982]; AKI due non-infectious etiology for cats and dogs, 59.9% [95% CI 0.532, 0.663; I2 = 51.0%, P = 0.0211]. CONCLUSION: Our findings suggest higher rates of overall mortality in cats and dogs with AKI due to non-infectious etiologies relative to infectious etiologies, and showed non-significant differences in terms of higher rates associated with dialysis compared to conservative management. Further investigations regarding optimal time to initiate dialysis and the development of clinical models to prognosticate the course of disease and guide optimal treatment initiation for less severe cases of AKI in cats and dogs is warranted.