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)

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)

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)

Inflammation: improving understanding to prevent or ameliorate kidney diseases

Abstract 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.

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.

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar "acute kidney injury" or "kidney disease" and "Bothrops"; on Lilacs and SciELO "kidney disease" or "acute kidney injury" and "Bothrops". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.(AU)

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar "acute kidney injury" or "kidney disease" and "Bothrops"; on Lilacs and SciELO "kidney disease" or "acute kidney injury" and "Bothrops". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.(AU)

Acute kidney failure following severe viper envenomation: clinical, biological and ultrasonographic aspects

Acute kidney injury (AKI) is a frequent complication of snakebite envenomation, which is still little known in sub-Saharan Africa. This study aims to describe the clinical, biological and ultrasonographic aspects of AKI following severe snakebite envenomation managed in the intensive care unit. Method: A prospective observational survey was performed in Benin over a period of 18 months. All patients suffering severe snakebite envenomation (SBE) were included. The diagnosis of AKI was made using the KDIGO criteria. Kidney ultrasound exam was performed in all patients to assess internal bleeding and morphological and structural abnormalities of the kidneys. Results: Fifty-one cases of severe SBE were included. All patients presented inflammatory syndrome and showed abnormal WBCT whereas bleeding was found in 46 of them (90%). The median time to hospital presentation was three days. The majority of patients were male (M/F sex ratio = 1.55) and the median age was 26. Sixteen patients (31%) showed AKI according to the KDIGO criteria. Severe AKI (KDIGO stage 2 and 3) was observed in three patients, including one stage 2 and two stage 3. Kidney ultrasound revealed three cases of kidney capsular hematoma (6%), two cases of kidney hypertrophy (3%), three cases of kidney injury (4%), two stage 1 KDIGO and one stage 2 KDIGO. Only one patient benefited from hemodialysis. All patients showing AKI recovered without sequels. The median duration of hospital stays was four days. Seven patients died (14%) including four among the 16 AKI patients. Antivenom has been administered to 41 patients (80%). The comparison between patients without and with AKI did not show any significant difference except gender (p = 10-2). Conclusion: AKI is a common complication of severe snakebite envenomation. Resulting from inflammatory and hemorrhagic disorders, AKI may prove to be a short-term life-threatening factor.(AU)

Acute kidney failure following severe viper envenomation: clinical, biological and ultrasonographic aspects

Acute kidney injury (AKI) is a frequent complication of snakebite envenomation, which is still little known in sub-Saharan Africa. This study aims to describe the clinical, biological and ultrasonographic aspects of AKI following severe snakebite envenomation managed in the intensive care unit. Method: A prospective observational survey was performed in Benin over a period of 18 months. All patients suffering severe snakebite envenomation (SBE) were included. The diagnosis of AKI was made using the KDIGO criteria. Kidney ultrasound exam was performed in all patients to assess internal bleeding and morphological and structural abnormalities of the kidneys. Results: Fifty-one cases of severe SBE were included. All patients presented inflammatory syndrome and showed abnormal WBCT whereas bleeding was found in 46 of them (90%). The median time to hospital presentation was three days. The majority of patients were male (M/F sex ratio = 1.55) and the median age was 26. Sixteen patients (31%) showed AKI according to the KDIGO criteria. Severe AKI (KDIGO stage 2 and 3) was observed in three patients, including one stage 2 and two stage 3. Kidney ultrasound revealed three cases of kidney capsular hematoma (6%), two cases of kidney hypertrophy (3%), three cases of kidney injury (4%), two stage 1 KDIGO and one stage 2 KDIGO. Only one patient benefited from hemodialysis. All patients showing AKI recovered without sequels. The median duration of hospital stays was four days. Seven patients died (14%) including four among the 16 AKI patients. Antivenom has been administered to 41 patients (80%). The comparison between patients without and with AKI did not show any significant difference except gender (p = 10-2). Conclusion: AKI is a common complication of severe snakebite envenomation. Resulting from inflammatory and hemorrhagic disorders, AKI may prove to be a short-term life-threatening factor.(AU)

MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model

Purpose: To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI.Methods: Serum from sepsis and healthy patients was collected, sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved caspase-3 and Bcl-2, cell viability, relative caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay. Results: MiR-106a was up-regulated in serum of sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells. Conclusion: MiR-106a aggravated LPS-induced inflammation and apoptosis of TCMK-1 cells via regulating THBS2 expression.(AU)

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)

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)

An experimental study of exenatide effects on renal injury in diabetic rats

Purpose:To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats.Methods:Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined.Results:Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05).Conclusions:Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.(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)

An experimental study of ascorbic acid effects in acute renal failure under general anesthesia

Purpose: To evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model. Methods: Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation. Results: NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p 0.001) and cast (p 0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III. Conclusions: The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.(AU)

SDMA E GGT URINÁRIA NA LESÃO RENAL AGUDA EM CÃES SÉPTICOS E SUA CORRELAÇÃO COM ACHADOS HISTOPATOLÓGICOS RENAIS

A lesão renal aguda (LRA) é definida como síndrome resultante da diminuição abrupta e persistente da taxa de filtração glomerular que culmina em altos índices de mortalidade e morbidade. Embora a fisiopatologia não esteja completamente esclarecida, a LRA é uma das principais complicações que ocorrem em quadros de sepse. Por esse motivo, considera-se relevante o estudo de biomarcadores não invasivos que permitam identificar de forma prematura e eficiente a LRA em pacientes com sepse. Uma condição potencial de sepse na medicina veterinária é a piometra, sendo os animais acometidos considerados bons modelos experimentais. Neste estudo prospectivo e cego utilizaram-se de 20 cadelas com piometra, consideradas sépticas, de acordo com a classificação SIRS (Síndrome da Resposta Inflamatória Sistêmica), atendidas junto ao hospital veterinário da UNESP- Jaboticabal e Universidade de Franca. Com base no grau histopatológico de lesão renal, as pacientes foram distribuídas em três grupos: discreto, moderado e severo. Os biomarcadores testados para avaliar a eficiência da predição de LRA foram creatinina sérica (p= 0,079), dimetilarginina simétrica sérica (SDMAs) (p=0,650), gama glutamil transferase urinária (GGTu) (p=0,093) e relação GGTu/creatinina urinária (uGGTC) (p=0,707). Não houve diferença estatística para nenhum dos biomarcadores avaliados em relação aos grupos e, portanto, verificou-se que tais marcadores não foram clinicamente úteis na identificação do grau de severidade de lesão renal aguda ao diagnóstico em cadelas acometidas por sepse. Sugere-se a validação de outros biomarcadores renais em pacientes sépticos comparando a LRA com a histopatologia renal.

Acute kidney injury (AKI) is defined as a syndrome resulting from the abrupt and persistent decrease in the glomerular filtration rate that culminates in high rates of mortality and morbidity. Although the pathophysiology is not completely understood, AKI is one of the main complications that occur in sepsis. For this reason, the study of non-invasive biomarkers is considered relevant to the early and efficient identification of AKI in patients with sepsis. A potential condition of sepsis in veterinary medicine is pyometra. The animals affected are considered good experimental models. In this prospective blind study, 20 female dogs with pyometra considered septic, according to the classification SIRS (Systemic Inflammatory Response Syndrome), were used. The bitches were attended at the veterinary hospital of UNESP- Jaboticabal and Universidade de Franca. The patients were divided into three groups based on the histopathological degree of kidney injury, divided into mild, moderate and severe. The tested biomarkers to assess the efficiency of AKI prediction were creatinine (p = 0.079), serum symmetric dimethylarginine (SDMA) (p =0,650), the urinary glutamyl transferase range (GGTu) (p = 0.093) and the ratio GGTu / urinary creatinine (GGtc) (p = 0.707). There was no statistical difference for any of the biomarkers evaluated in relation to the groups, therefore, they were not clinically useful in identifying the degree of severity of acute kidney injury, at the time of diagnosis in bitches affected by sepsis. The validation of other renal biomarkers in septic patients is suggested by comparing AKI with renal histopathology.

AVALIAÇÃO DE PERFIL HEMOSTÁTICO EM CÃES EM QUADRO DE INJÚRIA RENAL AGUDA NÃO SUBMETIDOS À TERAPIA DIALÍTICA

A injúria renal aguda (IRA) representa uma grande casuística na medicina veterinária e está associada à elevada mortalidade. Em humanos, sabe-se que os quadros de IRA podem levar a alterações hemostáticas, as quais podem aumentar o tempo de permanência do paciente em hospitalização e elevar a mortalidade. Entretanto, a ocorrência de distúrbios coagulatórios em cães com IRA ainda não é bem compreendida. O objetivo deste estudo foi avaliar o perfil hemostático de cães em IRA, devidamente estadiados e se esses pacientes apresentam distúrbios de hemostasia. Além disso, correlacionar as variáveis testadas com a intensidade da azotemia e com o risco de óbito. O estudo contou com 42 pacientes, sendo 14 no grupo controle, 14 no grupo IRIS III e 14 no grupo IRIS IV, de diferentes, sexos, raças e faixas etárias. Os marcadores hemostáticos testados foram Dímero-D, TP, TTPa, TT e fibrinogênio, sendo que foram comparados um kit para Dímero-D em humanos com um kit para cães. O Dímero-D e os demais marcadores hemostáticos apresentaram-se aumentados nos pacientes em IRA de estágios III e IV, porém não houve correlação entre esses marcadores e a intensidade da azotemia. Entretanto, o Dímero-D apresentou forte correlação positiva com as enzimas hepáticas e com a RPCU. Todos os marcadores hemostáticos testados apresentaram correlação positiva com o risco de óbito do paciente. Além disso, os dois testes para Dímero-D avaliados, foram eficazes e apresentaram correlação positiva. O aumento dos marcadores hemostáticos e Dímero-D e a correlação entre RPCU e Dímero-D, sugerem uma tendência ao estado de hipercoagulabilidade nos cães avaliados, com IRA em estágio III e IV. O Dímero-D apresentou forte correlação positiva com o risco de morte dos pacientes, evidenciando seu potencial como marcador de prognóstico.

Acute kidney injury (AKI) represents a large sample in veterinary medicine and is associated with a high mortality. In humans it is known that AKI can lead to hemostatic changes which can increase the length of stay of the patient in hospital and increase mortality. However, the occurrence of coagulation disorders in dogs with AKI is still not well understood. The aim of this study was to evaluate the hemostatic profile of dogs in AKI duly staged and whether these patients present hemostasis disorders. In addition, correlate the variables tested with the intensity of azotemia and the risk of death. The study included 42 patients, 14 in the control group, 14 in the IRIS group III and 14 in the IRIS group IV with different genders, races and age groups. The tested hemostatic markers were D-Dimer, TP, TTPa, TT and fibrinogen and a kit for D-Dimer in humans was compared with a kit for dogs. D-Dimer and other hemostatic markers were increased in patients with stage III and IV but there was no correlation between these markers and azotemia intensity. However, D-Dimer showed a strong positive correlation with liver enzymes and with UPCR. All tested hemostatic markers were positively correlated with the patient's risk of death. In addition, the two tests for D-Dimer evaluated were effective and showed a positive correlation. The increase in hemostatic and D-Dimer markers and the correlation between UPCR and D-Dimer suggest a tendency to a hypercoagulable state in the evaluated dogs, with IRIS stage III and IV. The D-Dimer showed a strong positive correlation with the risk of death of patients, showing its potential as a prognostic marker

ULTRASSONOGRAFIA MODO-B E DOPPLER DOS RINS DE CADELAS COM NEOPLASIA MAMÁRIA SUBMETIDAS À QUIMIOTERAPIA ADJUVANTE

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 dos fármacos quimioterápicos ainda impõem importantes limitações ao seu uso em cães. 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). Na medicina veterinária, a avaliação ultrassonográfica é rotineiramente 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. O objetivo do presente estudo foi avaliar, por meio da ultrassonografia modo-B e Doppler, as alterações morfológicas e hemodinâmicas nos rins de cadelas com neoplasias mamárias submetidas ao protocolo quimioterápico de associação entre a gencitabina e a carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto à raça e com idades entre 7 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). 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.

Breast neoplasms is the most frequently diagnosed cancer in canine females. Although surgery is frequently the chosen procedure for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have taken place in the field of cancer therapy, the systemic repercussions of chemotherapy drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and the preventive monitoring of patients are important to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in organs of the abdominal cavity. Acting in a complementary way to B-mode assessment, Doppler mapping is efficient in recognizing changes in vascular hemodynamics. The aim of this study is to evaluate, through mode B ultrasonography and Doppler, the morphological and hemodynamic changes caused in the kidneys of those animals with breast neoplasms submitted to the chemotherapeutic protocol of association between gemcitabine and carboplatin. Altogether, 13 canine females were monitored, regardless of breed and aged between 7 and 13 years. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after the completion of each cycle (T1). Results evidenced in mode B do not indicate morphological changes along the chemotherapy protocols, however, the dopplervelocimetric indexes showed statistical differences before (TO) and after (T1) the administration of drugs. Concluded that Doppler ultrasonography can be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs that are potentially causing kidney damage.