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.

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).

International renal interest society best practice consensus guidelines for intermittent hemodialysis in dogs and cats.

Intermittent hemodialysis (IHD) is an advanced adjunctive standard of care for severe acute kidney injury (AKI) and other indications. Most animals with AKI are managed medically, however, when the disease is severe, medical management may not control the consequences of the disease, and animals with a potential for renal recovery may die from the consequences of uremia before recovery has occurred. Extracorporeal therapies aid the management of AKI by expanding the window of opportunity for recovery of sufficient kidney function to become dialysis independent. Intermittent hemodialysis (IHD) was introduced into veterinary medicine over 50 years ago, however, updated guidelines for the delivery of IHD have not been published for several decades. To that end, the International Renal Interest Society (IRIS) constituted a Working Group to establish best practice guidelines for the safe and effective delivery of IHD to animals with indications for dialytic intervention. The IRIS Working Group generated 60 consensus statements and supporting rational for a spectrum of prescription and management categories required for delivery of IHD on designated intermittent dialysis platforms (i.e., AKI, chronic hemodialysis and intoxications). A formal consensus method was used to validate the recommendations by a blinded jury of 12 veterinarians considered experts in extracorporeal therapies and actively performing IHD. Each vote provided a level of agreement for each recommendation proposed by the Working Group. To achieve a consensus, a minimum of 75% of the voting participants had to "strongly agree" or "agree" with the recommendation.

International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.