Urinary heat shock protein-72: A novel marker of acute kidney injury and chronic kidney disease in cats.

Acute kidney injury (AKI) in cats is associated with high mortality, partially attributed to late recognition of the disease when using currently available markers. Feline chronic kidney disease (CKD) has a variable progression rate. This study aimed to evaluate the sensitivity and specificity of urinary heat shock protein-72 to urinary creatinine ratio (uHSP72:uCr) as a diagnostic and prognostic marker in feline AKI, and as a prognostic indicator in feline CKD. The study included 63 cats, divided into five groups: healthy controls (n=10), urethral obstruction (UO; n=7), CKD (n=15), AKI (16 cats) and acute decompensating CKD (ACKD; n=15). Median uHSP72:uCr (ng/mg) of healthy, UO, CKD, AKI and ACKD cats were 0.44 (range, 0.13-1.1), 1.96 (range, 0.64-11.9), 4.2ng/mg (range, 0.57-22.16), 3.2 (range, 0.42-10.91) and 7.0 (range, 1.2-20.96), respectively, and differed (P<0.001) among groups. uHSP72:uCr was significantly lower in the controls vs. the CKD, AKI and ACKD groups. Receiver operator characteristic analysis of uHSP72:uCr, including the AKI and control groups, showed an area under the curve of 0.93 (95% confidence interval, 0.84-1.00), indicating an excellent predictive performance for diagnosing AKI. A 0.54ng/mg cutoff point corresponded to 94% sensitivity and 70% specificity for diagnosing AKI. The median survival time of cats with CKD with low uHSP72:uCr was longer (P=0.036) than in those with high uHSP72:uCr (561 vs. 112 days, respectively). uHSP72:uCr is a highly sensitive, moderately specific marker of AKI in cats, and is associated with the survival of cats with CKD.

Characterization of kidney damage using several renal biomarkers in dogs with naturally occurring heatstroke.

Heatstroke is often associated with acute kidney injury (AKI). The objectives of this study were to characterize the kidney damage occurring in canine heatstroke using routine and novel biomarkers and to assess their diagnostic and prognostic performance. Thirty dogs with naturally occurring heatstroke were enrolled prospectively. Blood and urine specimens were collected at presentation, at 4 h post-presentation and every 12 h until discharge or death. The glomerular filtration rate (GFR) and electrolyte fractional excretion (FE) at 4 h post-presentation were also calculated, based on urinary clearances. AKI was further characterized by evaluating urine neutrophil gelatinase-associated lipocalin/creatinine ratio (UNGAL), urine retinol-binding protein/creatinine ratio (URBP), urine C-reactive protein/creatinine ratio (UCRP) and urine protein to creatinine ratio (UPC). These biomarkers were compared to those for 13 healthy dogs. Thirteen dogs (43%) died and 17 (57%) survived. Median serum creatinine concentration at presentation was 1.69 mg/dL (range, 0.5-4.7 mg/dL), while concurrent GFR was markedly decreased (median 0.60 mL/min/kg; range, 0.00-3.10 mL/min/kg). Median Na fractional excretion was 0.08 (range, 0.01-0.41) and was an accurate predictor of AKI (area under curve 0.89; 95% confidence intervals 0.76-1.00). Median UPC at presentation was 4.8 (range, 0.4-46.0). Median UCRP, URBP and UNGAL were increased in all dogs with heatstroke, and were mean 232, 133, and 1213-fold higher than healthy control dogs, respectively. In conclusion, although AKI occurs invariably in dogs with heatstroke, it is often subclinical at presentation. Damage occurs in both the renal tubules and the glomeruli. Novel kidney function tests for the characterization of renal injury and its severity are superior to conventional markers and could be used to facilitate early diagnosis of AKI.

A retrospective study of positive pressure ventilation in 58 dogs: indications, prognostic factors and outcome.

OBJECTIVES: To assess the usefulness of clinical and clinicopathological parameters as prognostic markers of survival in dogs undergoing positive pressure ventilation. METHODS: Retrospective study of case records of 58 client-owned dogs undergoing positive pressure ventilation. Dogs were divided into two groups; inadequate oxygenation due to pulmonary parenchymal disease (Group 1) and inadequate ventilation (Group 2). RESULTS: Median duration of positive pressure ventilation was 30 (range 10 to 136) hours. Survival rate was 32% (19 dogs). Survivors were significantly younger (P<0·005) and had significantly higher (P<0·002) median PaO2 /FiO2 ratio at 4 to 12 hours postinitiation of positive pressure ventilation, and immediately before weaning (P<0·006) compared to non-survivors. A receiver operator characteristics analysis of PaO2 /FiO2 immediately before weaning as predictor of survival had an area under the curve of 0·76 (95% confidence interval 0·54 to 0·97), with optimal cut-off point of 252 mmHg, corresponding to a sensitivity and specificity of 0·80 and 0·79, respectively. The survival rates of dogs with PaO2 /FiO2 less than 200 mmHg at 4 to 12 hours postinitiation of positive pressure ventilation, or immediately before weaning were 15% (3/20 dogs) and 6% (1/16 dogs), respectively. CLINICAL SIGNIFICANCE: The PaO2 /FiO2 ratio is an early prognostic indicator of successful weaning in dogs undergoing positive pressure ventilation.

Serum pepsinogen-A, canine pancreatic lipase immunoreactivity, and C-reactive protein as prognostic markers in dogs with gastric dilatation-volvulus.

BACKGROUND: Pepsinogens are proenzymes secreted by gastric chief cells. In humans, their serum concentrations reflect gastric mucosal morphological and functional status. OBJECTIVES: To evaluate serum canine pepsinogen-A (cPG-A), C-reactive protein (CRP), and canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with gastric dilatation-volvulus (GDV). ANIMALS: Sixty-six dogs presented with GDV and 79 healthy controls. METHODS: Blood was collected prospectively, and records retrospectively reviewed. RESULTS: Median cPG-A concentration was higher in GDV dogs (median, 397 µg/L; range, 37-5,410) compared to controls (median, cPG-A 304 µg/L; range, 18-848; P = .07). Mortality rate in GDV dogs was 22.7%. In nonsurvivors of GDV, median cPG-A was higher compared to survivors (median, 746 µg/L; range, 128-5,409 versus median, 346; range, 36-1,575, respectively; P = .003). The proportion of dogs with increased cPG-A increased with gastric wall damage score (P = .007). An ROC analysis of cPG-A as a predictor of death showed an area under the curve (AUC) of 0.75, higher than lactate (AUC 0.66), and corresponded to a sensitivity and specificity of 53% and 88%, respectively. CRP was increased in 48 dogs (75%), cPLI was >200 µg/L in 26 dogs (39.4%) and >400 µg/L in 12 dogs (18.2%) but both analytes had no association with outcome. CONCLUSIONS: Presurgical cPG-A concentration was positively and significantly associated with gastric wall lesion severity, but, based on ROC analysis, it was only a moderate outcome predictor. CRP and cPLI were commonly increased in dogs with GDV.

Accidental fatal aflatoxicosis due to contaminated commercial diet in 50 dogs.

Aflatoxins, produced by Aspergillus spp., are toxic contaminants of stored grain. This study describes 50 dogs presented with foodborne aflatoxicosis. Common clinical signs included lethargy (78%), vomiting (76%), anorexia (74%), icterus (66%), depression (66%), melena (60%), haematuria (36%) and diarrhoea (36%). Common laboratory abnormalities included increased activities of aspartate aminotransferase (86%), alkaline phosphatase (84%) and alanine aminotransferase (79%), hypoantithrombinaemia (86%), prolonged prothrombin (PT, 82%) and activated partial thromboplastin times (aPTT, 80%), hyperbilirubinaemia (73%), hypocholesterolaemia (60%) hypoalbuminemia (47%) and thrombocytopenia (42%). Non-survivors had longer PT and aPTT and lower antithrombin (P<0.001) at presentation compared to survivors (23.8s vs.10.5; 37.9 vs.17.6s and 5% vs. 54%, respectively). Hyperbilirubinaemia (>56.6 µmol/L) and albumin concentration <32.5 g/L at presentation were risk factors for mortality (P<0.0001). Common complications included disseminated intravascular coagulation (58%), hepatic encephalopathy (35%) and acute kidney injury (4%). The mortality rate was 68%, suggesting that dogs with aflatoxicosis have poor prognosis.

Peripheral nucleated red blood cells as a prognostic indicator in heatstroke in dogs.

BACKGROUND: Heatstroke in dogs is often fatal and is associated with a high prevalence of secondary complications. Peripheral nucleated red blood cells (NRBC) occur in dogs with heatstroke, but their association with complications and the outcome is unclear. HYPOTHESIS: Peripheral NRBC are common in dogs with heatstroke and have prognostic significance. ANIMALS: Forty client-owned dogs with naturally occurring heatstroke. METHODS: Prospective, observational study. Dogs were followed from presentation to discharge or death. Serum biochemistry and coagulation tests were performed at presentation. CBC and evaluation of peripheral blood smears were performed at presentation and every 12 hours. The relative and the absolute NRBC numbers were calculated. RESULTS: Presence of NRBC was observed in 36/40 (90%) of the dogs at presentation. Median relative and absolute NRBC were 24 cells/100 leukocytes (range 0-124) and 1.48 x 10(3)/microL (range 0.0-19.6 x 10(3)/microL), respectively. Both were significantly higher in nonsurvivors (22) versus survivors (18) and in dogs with secondary renal failure and DIC versus those without these complications. Receiver operator curve analysis of relative NRBC at presentation as a predictor of death had an area under curve of 0.92. A cut-off point of 18 NRBC/100 leukocytes corresponded to a sensitivity and specificity of 91 and 88% for death. CONCLUSIONS AND CLINICAL IMPORTANCE: Relative and absolute numbers of peripheral NRBC are clinically useful, correlate with the secondary complications, and are sensitive and specific markers of death in dogs with heatstroke, although they should never be used as a sole prognostic indicator nor should they replace clinical assessment.

Pathological findings in dogs with fatal heatstroke.

Eleven dogs with fatal heatstroke were examined grossly and histopathologically post mortem. All showed multi-organ haemorrhagic diathesis with coagulative necrosis. Hypaeremia and diffuse oedema were observed in the skin (eight dogs), lungs (11), brain (11) and bone marrow (one). Congestion of the splenic pulp (10 dogs) and hepatic sinusoids (nine) was also noted. Necrosis was observed in the mucosa of the small intestine (seven dogs), large intestine (eight), renal tubular epithelium (nine), hepatic parenchyma (eight) and brain neural tissue (four). The results showed that naturally occurring, fatal canine heatstroke induces acute multiple organ lesions affecting most body systems, and suggest that the more prevalent lesions include haemorrhagic diathesis, microthrombosis and coagulative necrosis. These are probable sequels of hyperthermia-induced disseminated intravascular coagulation and systemic inflammatory response syndrome, which lead to multi-organ dysfunction and death.

Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog.

A nine-year-old Labrador retriever dog was admitted to the emergency unit of the Hebrew University Veterinary Teaching Hospital with acute-onset tremors and coma. It had recently ingested a large quantity of phenobarbital and had a high serum phenobarbital concentration. On this basis, a diagnosis of acute phenobarbital intoxication was made. Significant leucopenia, thrombocytopenia and mild anaemia developed on the third day after admission. The leucopenia resolved on day 6 and the thrombocytopenia on day 13. The red blood cell count remained low for the next month. The dog was discharged on day 13 at which time it was ambulatory but weak. It was completely recovered clinically eight days later. In summary, high levels of serum phenobarbital as a result of acute intoxication induced pancytopenia, which improved when the serum phenobarbital level was normalised.

Seroprevalence of Anaplasma phagocytophilum among healthy dogs and horses in Israel.

The presence of reacting antibodies to Anaplasma phagocytophilum has previously been demonstrated in Israel, both in humans and the golden jackal (Canis aureus syriacus). This study was undertaken to determine the seroprevalence of A. phagocytophilum antibodies in two additional potential hosts, domestic dogs and horses in order to investigate the possibility of exposure to the organism in Israel. Of 195 dogs tested, 9% were seroreactive with A. phagocytophilum antigen and 30% were seroreactive to Ehrlichia canis. Twenty-nine percent of the dogs seropositive for E. canis were also reactive to A. phagocytophilum. Two dogs had immunofluorescence antibody (IFA) antibody titres for A. phagocytophilum greater than E. canis. The equine serological survey (n = 300) revealed no seroreactive horses. The results presented in this study suggest that dogs in Israel could have been accidentally exposed to A. phagocytophilum, for example by ticks carried on migrating birds, however, the possibility of cross-reaction with E. canis should also be considered. In spite of the high prevalence of ticks on horses in Israel during the summer months, no evidence for exposure to A. phagocytophilum was apparent.

Disseminated aspergillosis in two dogs in Israel.

Aspergillus terreus, normally a soil or plant saprophyte, causes disseminated systemic infection, involving primarily the skeletal and the cardiopulmonary system in humans and dogs.(1, 2) We describe two cases of German shepherd dogs that were referred to Koret School of Veterinary Medicine Teaching Hospital with a history of anorexia and weakness. Case 1 suffered from neurological deficits, paraparesis and lumbar pain whereas case 2 suffered from unilateral uveitis and exophthalmus. Both dogs were treated symptomatically, but deteriorated progressively despite therapy and were therefore euthanised. Necropsy revealed disseminated aspergillosis, and numerous organs had multiple, miliary, white-yellow foci. Microscopically, these were identified as granulomas, containing fungal hyphae. Affected tissue included brain, heart, kidneys, spleen, lymph nodes and bones (case 2). Aspergillus terreus was isolated from different organs and from urine culture. We suggest that disseminated aspergillosis should be considered as a differential diagnosis in German shepherd dogs presenting with ocular disease, neurological deficits, spinal column pain, urinary system disorders, and radiographic evidence of skeletal and/or respiratory pathology.

L-thyroxine responsive cricopharyngeal achalasia associated with hypothyroidism in a dog.

An eight-year-old, male boxer dog was presented with a one-month history of hindlimb weakness followed by compulsive ineffective drinking, dysphagia, regurgitation and nasal reflux during drinking. A neurological examination revealed weakness and conscious proprioception deficits in both hindlimbs with normal spinal reflexes. The dog's swallowing function was examined by fluoroscopy. This showed normal prehension of the barium paste, bolus formation and contraction of the pharyngeal muscle, but no opening of the upper oesophageal sphincter was detected. A serum thyroid stimulating hormone level of 0.402 ng/dl and serum total T4 of 0-01 microg/dl were determined. The dog fully recovered one month after L-thyroxine therapy. The association found between cricopharyngeal achalasia and hypothyroidism suggests that hypothyroidism should be included in the list of differential diagnoses for dogs with cricopharyngeal achalasia.

Severe tongue necrosis associated with pine processionary moth (Thaumetopoea wilkinsoni) ingestion in three dogs.

The pine processionary moth (Thaumetopoea wilkinsoni) is an insect of medical significance in the eastern Mediterranean. This report describes three exposure cases in dogs due to ingestion of this moth's caterpillars in Israel. All three dogs were observed in direct contact with caterpillars or pinecones in infested gardens. The disease course and progression of signs were acute in all three cases, and included vomiting and severe tongue swelling. Physical examination findings included hyperthermia, tachypnoea, respiratory distress, cyanosis and tongue oedema, labial angioedema, ptyalism, bilateral submandibular lymphadenomegaly and conjunctivitis. Severe tongue necrosis and sloughing of its distal portion occurred 2-5 days after admission to the hospital. All dogs recovered and were discharged within 2-7 days of admission. Two staff members, attending one of the dogs, experienced an itchy rash and wheals on their arms, wrists and necks. To the best of our knowledge, this should be the first report of severe oral lesions and tongue necrosis due to contact with T. wilkinsoni caterpillars.