A longitudinal study of the blood and urine metabolome of Vipera berus envenomated dogs.

Envenomation of dogs by the common European adder (Vipera berus) is associated with high morbidity. The cytotoxic venom of Vipera berus contains enzymes with the potential to cause acute kidney injury, among other insults, however robust biomarkers for such effects are lacking. A prospective observational follow-up study of naturally envenomated dogs and controls was conducted to fill knowledge gaps regarding canine Vipera berus envenomation, attempt to identify novel biomarkers of envenomation and related kidney injury, and elucidate potential long-term effects. Blood and urine samples were analyzed with a global metabolomics approach using liquid chromatography-mass spectrometry, uncovering numerous features significantly different between cases and controls. After data processing and feature annotation, eight features in blood and 24 features in urine were investigated in order to elucidate their biological relevance. Several of these are associated with AKI, while some may also originate from disturbed fatty acid ß-oxidation and soft tissue damage. A metabolite found in both blood and a venom reference sample may represent identification of a venom component in case dogs. Our findings suggest that envenomated dogs treated according to current best practice are unlikely to suffer permanent injury.

Acute kidney injury and liver disease in an American bulldog with suspected leptospirosis.

A 6-year-old spayed female American bulldog was brought to a veterinary clinic with a 3-day history of vomiting, lethargy, anorexia, icterus, hemorrhagic diarrhea, and oliguria. The dog's clinical signs, complete blood (cell) count, serum biochemistry, urinalysis, and diagnostic imaging were indicative of acute kidney injury and acute hepatopathy consistent with leptospirosis. Treatment for leptospirosis was initiated but, due to the dog's lack of response and progression of clinical signs, euthanasia was ultimately elected after 3 d of hospitalization. The dog tested negative for Leptospira spp. on ELISA; urine, blood, and tissue PCRs; and immunohistochemistry. This case demonstrates that confirmation of leptospirosis can be challenging, even in an animal with the expected clinical presentation. Therefore, limitations of the diagnostic tests available, as well as the possibility of other, less likely differential diagnoses such as toxicosis, must be considered.

Lésion rénale aiguë et maladie hépatique chez un bouledogue américain avec leptospirose suspectée. Une femelle bouledogue américain stérilisée âgée de 6 ans a été présenté à une clinique vétérinaire avec une histoire d'une durée de 3 jours de vomissement, léthargie, anorexie, ictère, diarrhée hémorragique et oligurie. Les signes cliniques de la chienne, un comptage cellulaire sanguin complet, une biochimie sérique, une analyse d'urine et de l'imagerie diagnostique étaient indicateur de lésion rénale aiguë et d'hépatopathie aiguë compatibles avec la leptospirose. Un traitement pour la leptospirose a été instauré mais, étant donné l'absence de réponse de l'animal et la progression des signes cliniques, l'euthanasie a finalement été décidée après 3 jours d'hospitalisation. L'animal s'est avéré négatif par ELISA pour Leptospira spp.; l'urine, le sang et les tissus étaient également négatifs par PCR; et par immunohistochime. Ce cas illustre le fait que la confirmation de la leptospirose peut représenter un défi, même chez un animal avec la présentation clinique attendue. Ainsi, les limites des tests diagnostiques disponibles, de même que la possibilité d'autres diagnostics différentiels moins probables, tel qu'une toxicose, doivent être considérés.(Traduit par Dr Serge Messier).

Retrospective evaluation of 22 dogs with leptospirosis treated with extracorporeal renal replacement therapies (2018-2021).

BACKGROUND: Outcomes of dogs with acute kidney injury secondary to leptospirosis (AKI-L) treated using renal replacement therapies (RRT) are poorly characterized. HYPOTHESIS/OBJECTIVES: Describe survival to discharge, short (≤30 days) and long-term (≥6 months) outcomes of AKI-L dogs receiving RRT and determine if there is a significant difference in maximum blood urea nitrogen (maxBUN), maximum creatinine (maxCr), maximum bilirubin (maxBili) and the number of body systems affected between survivors and non-survivors. ANIMALS: Twenty-two client-owned dogs with AKI-L receiving RRT. METHODS: Retrospective medical record review of dogs with AKI-L that received RRT between 2018 and 2021. RESULTS: Sixteen of 22 (73%) dogs survived to discharge. Of the survivors, 13 (81%) were alive >30 days from discharge and 12 (75%) were alive at 6 months from discharge. Factors significantly higher in non-survivors included number of body systems affected (survivors: 1 (19%), 2 (50%), 3 (25%) and 4 (6%) vs non-survivors: 3 (33.3%), and 4 (66.7%); P = .01) and median maxBili (survivors: 1.9 mg/dL; range, 0.1-41.6 vs non-survivors: 21.0 mg/dL; range, 12.3-38.9; P = .02). There was no significant difference in median maxBUN (survivors: 153.0 mg/dL; range, 67-257 vs non-survivors: 185.5 mg/dL; range, 102-218; P = .44) and median maxCr (survivors: 9.8 mg/dL; range, 6.2-15.9 vs non-survivors: 9.8 mg/dL; range, 8.4-13.5; P = .69) between survivors and non-survivors. CONCLUSIONS AND CLINICAL IMPORTANCE: Regardless of azotemia severity, dogs with AKI-L receiving RRT have a good survival rate to discharge. The number of body systems affected and hyperbilirubinemia might be associated with worse outcomes.

Severe glomerular fibrin thrombosis in a dog.

Here, we present a case of severe glomerular fibrin thrombosis in a dog with lymphoma. A 3-year-old neutered male Chihuahua presented with acute kidney injury, hypoalbuminemia, and transudate ascites. The dog showed symmetric enlargement of the spleen, which was diagnosed as B-cell lymphoma based on cytology and polymerase chain reaction tests. The dog died after intensive care, and the kidneys were removed for histopathological examination. Light microscopy, immunofluorescence, and electron microscopy analyses were performed for renal pathology; however, the findings did not support the evidence of protein-losing nephropathy. Instead, the endocapillary accumulation of fibrin thrombi was prominent in most glomeruli. A diagnosis of severe glomerular fibrin thrombosis was established, and hypoalbuminemia was considered the underlying cause of kidney damage.

Acute pyelonephritis in cats is frequently caused by Escherichia coli resistant to potentiated penicillins but has a better prognosis than other causes of acute kidney injury.

OBJECTIVE: To describe the clinical findings, microbiological data, treatment, and outcome of a population of cats with suspected acute pyelonephritis (APN). ANIMALS: 32 client-owned cats. CLINICAL PRESENTATION AND PROCEDURES: Retrospective case series from 2 veterinary teaching hospitals between January 1, 2014, and December 31, 2020. Cats were included if they had a positive bacterial urine culture and a clinical diagnosis of acute kidney injury. RESULTS: Older female cats with underlying chronic kidney disease have a higher probability to develop bacterial culture-positive acute kidney injury or APN. Escherichia coli was the most commonly cultured bacterial species, and E coli isolates with susceptibility testing were resistant to amoxicillin-clavulanate but susceptible to fluoroquinolones or third-generation cephalosporins. Of the 20 cats with available follow-up information in the medical record, 14 were alive at 3 months after hospital discharge. Markers of renal function including creatinine (P = .008), BUN (P = .005), and phosphorus (P < .001) at the time of presentation were all higher in nonsurvivors compared with survivors. CLINICAL RELEVANCE: The survival rate with feline APN is higher than previous reports of acute kidney injury when all etiologies are considered. Nonsurvivors had more pronounced azotemia upon initial presentation. Amoxicillin-clavulanate was a poor empirical antimicrobial in this cohort based on the microbiological data.

Evaluation of the clinical outcome of hypercalcemia of malignancy and concurrent azotemia in dogs with lymphoma.

BACKGROUND: Hypercalcemia of malignancy (HM) secondary to lymphoma in dogs has the potential to cause renal injury. HYPOTHESIS/OBJECTIVES: Characterize outcomes related to acute kidney injury (AKI) secondary to HM. We hypothesized that dogs do suffer AKI regardless of HM severity at the time of lymphoma diagnosis or relapse. ANIMALS: Retrospective study. Twenty-nine dogs with lymphoma, HM, and azotemia (International Renal Interest Society [IRIS] grade II or higher AKI) that underwent chemotherapy were identified at 2 veterinary institutions. METHODS: Logistic regression and descriptive statistical analysis were performed to evaluate data for potential prognostic factors. RESULTS: After initiating treatment, resolution of hypercalcemia and azotemia occurred in 100% (29/29) and 79.3% (23/29) of dogs, respectively. Resolution of azotemia was influenced by serum creatinine concentration (odds ratio [OR], 0.148; Confidence interval [CI], 0.03-0.734; P = .02) and total hypercalcemia (OR, 0.36; CI, 0.14-0.93; P = .04) at diagnosis, whereas blood urea nitrogen concentration, IRIS grade, sex, and whether or not dogs were hospitalized were not significant factors. At data analysis, 13.8% (4/29) of dogs were alive or lost to follow-up. Of those dead, 4 dogs (15%) had renal disease at the time of death, 2/4 having concurrent lymphoma progression. CONCLUSIONS AND CLINICAL IMPORTANCE: Although AKI may be of clinical concern in dogs with HM secondary to lymphoma at diagnosis, death secondary to renal impairment appears to be infrequent.

Retrospective evaluation of the clinical course and outcome of zinc toxicosis due to metallic foreign bodies in dogs (2005-2021): 55 cases.

OBJECTIVE: To describe the overall clinical course of zinc toxicosis in dogs including source, time to source control, incidence of hemolytic anemia, acute liver injury (ALI), acute kidney injury (AKI), and pancreatitis. DESIGN: Retrospective case series from 2005 to 2021. SETTING: Six university veterinary teaching hospitals. ANIMALS: Fifty-five client-owned dogs with known zinc toxicosis due to metallic foreign body (MFB) ingestion. MEASUREMENTS AND MAIN RESULTS: The most common source of zinc was US pennies minted after 1982 (67.3%). Forty-five of 55 (81.8%) dogs survived and 10 of 55 (18.2%) died or were euthanized. Median length of hospitalization for survivors and nonsurvivors was 3 days. The most common clinical sequelae of zinc toxicosis were anemia (87%), ALI (82%), coagulopathy (71%), thrombocytopenia (30.5%), AKI (26.9%), and acute pancreatitis (5.5%). Most dogs (67.3%) required blood products and 83% of dogs achieved a stable HCT or PCV in a median of 24 hours after MFB removal. The median duration of illness prior to presentation was 48 hours for both survivors and nonsurvivors and there was no impact of time to presentation on the incidence of ALI, AKI, or pancreatitis. CONCLUSIONS: Zinc toxicosis secondary to MFB ingestion should be considered a differential diagnosis for dogs with gastrointestinal signs, hemolytic anemia, ALI, hemostatic abnormalities, AKI, and pancreatitis. AKI may be a more common sequela of zinc toxicosis than previously suspected. Acute pancreatitis is a rare but potentially serious sequela to zinc toxicosis.

Diagnostic utility of two-dimensional shear wave elastography in nephropathic dogs and its correlation with renal contrast-enhanced ultrasound in course of acute kidney injury.

Aims of our study were to evaluate the feasibility and diagnostic value of two-dimensional shear wave elastography in dogs with acute kidney injury, chronic kidney disease, and acute on chronic kidney disease, its correlation with renal functional (creatinine, urea), and prognostic parameters (serum calcium-phosphorus product, urinary output), and with contrast-enhanced ultrasound (qualitative and quantitative evaluation). The study was prospective. A group of healthy (Group A) and a group of nephropathic dogs (Group B) were included. Shear wave elastography was performed on the left kidney of the subjects of both groups; contrast-enhanced ultrasound was performed only in dogs with acute kidney injury and acute on chronic kidney disease. Sixty-four dogs were included (Group A, n=24; Group B, n=40). The renal stiffness values were significantly higher in Group B than Group A; optimal cut-off stiffness values for detection of renal pathology were: ≥1.51 m/sec (area under the curve, 0.84; 95% confidence interval 0.74-0.94) and ≥6.75 kPa (area under the curve, 0.84; 95% confidence interval 0.73-0.94). For contrast-enhanced ultrasound, a significant positive correlation was found between renal stiffness, area under the curve, and wash-out area under the curve values of cortex quantitative analysis. No correlations were found between renal stiffness and renal functional and prognostic parameters. Shear wave elastography showed diagnostic utility to detect renal abnormalities in dogs with acute kidney injury, chronic kidney disease and acute on chronic kidney disease, however, it could not differentiate between these different nephropathies.

Retrospective evaluation of acute kidney injury in horses treated with nonnitrogenous bisphosphonates (2013-2020): 8 cases.

OBJECTIVE: To describe a population of horses with acute kidney injury (AKI) following administration of bisphosphonates including clinical signs, clinicopathologic data, treatment, and outcome. DESIGN: Retrospective study from August 2013 to July 2020. SETTING: Veterinary university teaching hospital. ANIMALS: Eight adult horses with AKI following administration of nonnitrogenous bisphosphonates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five horses received intramuscular clodronate (5/8; 62.5%) and 3 horses received intravenous tiludronate (3/8; 37.5%). Six horses (6/8; 75%) received concurrent nonsteroidal anti-inflammatory drugs. The most common initial presenting complaint was poor appetite (6/8; 75%), followed by abnormal urination (2/8; 25%). At the time of initial evaluation, the mean serum or plasma creatinine was 451.72 ± 190.06 µmol/L (5.11 ± 2.15 mg/dL) and BUN was 18.84 ± 8.85 mmol/L (52.75 ± 24.77 mg/dL). Five horses (5/6; 83.3%) had either an increased number of red blood cells (n = 4) or hemoprotein (n = 1) in the urine. All horses were treated with IV isotonic, balanced crystalloids either as a bolus, continuous rate infusion, or a combination of the 2. Seven horses (7/8; 87.5%) survived the initial episode of AKI and 1 horse (1/8; 12.5%) was euthanized. Of the 7 surviving horses, 2 horses (2/7; 28.5%) went on to develop chronic renal dysfunction. Warmblood breeds were overrepresented in the AKI group (P = 0.008; odds ratio: 11.5, 95% confidence interval: 1.8-72.1), when compared to horses that received bisphosphonates during the study period and did not develop AKI. CONCLUSIONS: Bisphosphonate administration, with or without concurrent nonsteroidal anti-inflammatory drugs, can be associated with AKI in horses. Serum creatinine should be monitored prior to and following bisphosphonate treatment to minimize this risk. Further evaluation of renal function is warranted in horses that develop clinical signs of poor appetite, lethargy, or altered urination in the days following bisphosphonate treatment.

The utility of clinicopathological findings and point-of-care ultrasound in increasing the index of suspicion of ureteral obstruction in azotaemic cats presenting to the emergency room.

OBJECTIVES: Ureteral obstruction is a common post-renal cause of azotaemia in cats. The objective of this study was to describe clinicopathological and point-of-care ultrasound findings in azotaemic cats that may increase the index of suspicion of ureteral obstruction. MATERIALS AND METHODS: A retrospective case-control study was conducted of azotaemic cats presenting to the emergency room of a referral teaching hospital. Cats were included if they were azotaemic and had point-of-care ultrasound and formal ultrasound performed. Cats were grouped into obstructed and non-obstructed groups based on formal specialist ultrasound and pyelography. Point-of-care ultrasound findings were described, including renal size and symmetry, renal pelvis dilation, perinephric fluid, and visualisation of the proximal ureter or calculi. Univariate analysis was performed to identify historical, biochemical and point-of-care ultrasound findings associated with ureteral obstruction before multivariate analysis. RESULTS: One hundred twenty-two azotaemic cats met the inclusion criteria. Seventy-four cats were included in the obstructed azotaemic group and 48 cats in the non-obstructed azotaemic groups. Point-of-care ultrasound abnormalities were detected in 60 of 74 (81.1%) obstructed cats and 18 of 48 (37.5%) non-obstructed cats. Renal pelvis dilation (odds ratio 38.8; 95% confidence interval 2.9 to 515), hyporexia (odds ratio 5.9; 95% confidence interval 1.15 to 30.13), hypercalcaemia (odds ratio 16.6; 95% confidence interval 1.2 to 223.0) and hypokalaemia (odds ratio 21.7; 1.33 to 354.62) were more likely to be associated with ureteral obstruction than non-obstructive disease. CLINICAL SIGNIFICANCE: Point-of-care ultrasound abnormalities are documented frequently in azotaemic cats with ureteral obstruction. Cats with renal pelvis dilation were 39 times more likely to have ureteral obstruction than non-obstructive acute kidney injury.

Acute kidney injury is common in dogs with septic peritonitis and is associated with increased mortality.

OBJECTIVE: To identify the frequency of and risk factors for acute kidney injury (AKI) in dogs undergoing abdominal surgery for septic peritonitis, and to evaluate outcome and kidney-related risk factors for survival to discharge in those dogs. ANIMALS: 77 dogs that underwent abdominal surgery for septic peritonitis. METHODS: Medical records of dogs that underwent surgery for septic peritonitis from 2012 through 2022 were reviewed. Data regarding signalment, clinical and biochemical findings at presentation, blood creatinine concentration throughout hospitalization, surgery characteristics, postoperative monitoring, and outcome were collected. Dogs were classified based on occurrence of AKI and whether they presented with or developed AKI in-hospital. Perioperative risk factors were evaluated, and outcomes were compared with univariable logistic regression. RESULTS: 31 dogs (40.3%) had AKI diagnosed; 18/77 (23.4%) dogs presented with AKI, 11 (61.1%) of which had it postoperatively, and 13/77 (16.9%) dogs developed AKI postoperatively. Significant factors for presenting with AKI included increasing baseline respiratory rate (OR 2.5 for every 10 beats per minute higher), decreasing systolic blood pressure (OR 0.8 for every 10 mm Hg higher), and increasing body condition score (OR 2.2 for every score greater). No significant factors for developing AKI postoperatively were identified after multiple comparisons adjustment. Sixteen dogs (20.8%) did not survive to discharge; 12 (75.0%) had AKI and 4 (25.0%) did not. Dogs with AKI had decreased odds of survival to discharge (OR 0.2). CLINICAL RELEVANCE: AKI was common in dogs with septic peritonitis and was a significant risk factor for survival to discharge. Clinical surveillance of AKI is critical in this population.

Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin.

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.

Urine Output Monitoring and Acute Kidney Injury in Non-mammalian Exotic Animal Critical Care.

Acute kidney injury (AKI) is a sudden, severe decrease in kidney function which can occur in any species. There are various causes of AKI, some of which are seen in domestic species and some that are unique to birds, reptiles, and amphibians. These species present unique challenges with AKI management, such as differences in anatomy and physiology, intravenous and urinary catheterization, repeated blood sampling, and their tendency to present in advanced states of illness. This article will discuss AKI, diagnosis, treatment, and prognosis for non-mammalian exotic species.

Urine Output Monitoring and Acute Kidney Injury in Mammalian Exotic Animal Critical Care.

Acute kidney injury (AKI) is a sudden, severe decrease in kidney function which can occur in any species. There are various causes of AKI, some of which are seen in domestic species and some that are unique to exotics. Exotic animals present unique challenges with AKI management such as differences in anatomy and physiology, intravenous and urinary catheterization, repeated blood sampling, and their tendency to present in advanced states of illness. This article will discuss AKI, diagnosis, treatment, and prognosis for exotic companion mammals. The following article will discuss the same in non-mammalian patients.

Cross-sectional characterization of renal function in cats with caudal stomatitis.

OBJECTIVES: The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats. METHODS: A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a t-test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test. RESULTS: Relative to the control group, cats in the CS group had significantly lower serum creatinine (P <0.001) and albumin concentrations (P <0.001), urine specific gravity (P = 0.024) and hematocrit (P = 0.003), and higher serum phosphorus (P <0.001), potassium (P <0.001) and globulin concentrations (P <0.001), white blood cell count (P <0.001) and urine protein:creatinine ratio (P = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups. CONCLUSIONS AND RELEVANCE: The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.