Query: injury of dogs

title: Association between the intrarenal renin angiotensin system and renal injury in chronic kidney disease of dogs and cats.
abstract: The association of renin and angiotensin II, which are potent components of the renin angiotensin system, with the severity of chronic renal disease was investigated immunohistochemically in dogs and cats. Immunoreactivities of renin and angiotensin II were evaluated quantitatively, and their correlations with the degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration and interstitial fibrosis were statistically analyzed. Immunoreactivities for renin were detected in afferent arteries in both dogs and cats. The score of renin positive signals showed no correlation with plasma creatinine concentration or any of the histopathological parameters, except for the diameter of glomeruli in dogs. Immunoreactivities for angiotensin II were detected in tubules (primarily proximal tubules) and interstitial mononuclear cells in both dogs and cats. The score of tubular angiotensin II correlated with glomerulosclerosis and cell infiltration in cats but not in dogs. The score of interstitial angiotensin II correlated with plasma creatinine concentration, glomerulosclerosis, cell infiltration and fibrosis in dogs and with glomerulosclerosis and cell infiltration in cats. In conclusion, the results of the study suggest that intrarenal renin angiotensin system is correlated with the severity of kidney disease, with the underlying mechanism differing between dogs and cats.

title: Plasma Symmetric Dimethylarginine Concentration in Dogs with Acute Kidney Injury and Chronic Kidney Disease
abstract: Symmetric dimethylarginine (SDMA) is considered a biomarker for early detection of renal dysfunction in human patients with acute kidney injury (AKI) At present, no studies exist analyzing the relevance of SDMA in dogs with AKI. Hypothesis/objectives SDMA would correctly identify dogs with renal disease but would not be able to differentiate between AKI and CKD. Animals Eighteen healthy control dogs, 48 dogs with AKI, and 29 dogs with CKD.  Prospective study. Dogs with kidney disease were categorized as having AKI or CKD according to the history, clinical signs, laboratory findings, and results of diagnostic imaging. Plasma SDMA concentration was measured by IDEXX Laboratories. SDMA/creatinine ratio was calculated in dogs with AKI or CKD.  Median SDMA concentrations were 8.5 mg/dL (6 12 mg/dL) 39.5 mg/dL (8 >100 mg/dL) and 35 mg/dL (12 >100 mg/dL) in healthy, AKI, and CKD, respectively. SDMA concentrations were significantly higher in dogs with AKI (P .0001) or CKD (P .0001) in comparison with healthy dogs. Median SDMA/creatinine ratio in dogs with AKI and CKD was 6.5 (1.7 20.9) and 10 (2.4 33.9) (P .0004) respectively. Although there was overlap of the SDMA/creatinine ratio in dogs with AKI or CKD, it was significantly higher in dogs with CKD compared to dogs with AKI (P .0004) Conclusions and Clinical Importance In this population, SDMA was suitable for identifying dogs affected by AKI or CKD, but could not differentiate between them.

title: Fasiglifam (TAK 875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury
abstract: &NA; Fasiglifam (TAK 875) a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK 875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations. Repeat dose studies determined that TAK 875 caused a dose dependent increase in serum total BA in rats and dogs. Additionally, there were dose dependent increases in both unconjugated and conjugated individual BAs in both species. Rats had an increase in serum markers of liver injury without correlative microscopic signs of tissue damage. Two of 6 dogs that received the highest dose of TAK 875 developed liver injury with clinical pathology changes, and by microscopic analysis had portal granulomatous inflammation with neutrophils around a crystalline deposition. The BA composition of dog bile also significantly changed in a dose dependent manner following TAK 875 administration. At the highest dose, levels of taurocholic acid were 50% greater than in controls with a corresponding 50% decrease in taurochenodeoxycholic acid. Transporter inhibition by TAK 875 may cause liver injury in dogs through altered bile BA composition characteristics, as evidenced by crystalline deposition, likely composed of test article, in the bile duct. In conclusion, a combination of in vitro and in vivo evidence suggests that BA transporter inhibition could contribute to TAK 875 mediated liver injury in dogs.

title: Retrospective cohort study on the incidence of acute kidney injury and death following hydroxyethyl starch (HES 10% 250/0.5/5:1) administration in dogs (2007 2010)
abstract: To determine the incidence of in hospital adverse outcomes including acute kidney injury (AKI) and death in a population of dogs admitted to the intensive care unit (ICU) receiving 10% hydroxyethyl starch (HES) [250/0.5/5:1] compared with the general ICU population, while controlling for illness severity.   Veterinary teaching hospital.  Consecutive sample of dogs receiving HES (n 180) were compared with a randomly selected sample of dogs (n 242) admitted to the ICU over the same period.  None MEASUREMENTS AND MAIN RESULTS AKI was defined as an at least 2 fold increase in baseline creatinine concentration or new onset of oliguria/anuria persisting for =12 hours. The primary outcome was a composite of in hospital death or AKI. Unadjusted and adjusted analysis controlling for illness severity using the acute patient physiologic and laboratory evaluation (APPLEfast score and other confounders was performed. HES was administered either as incremental boluses (median dose 8.2 mL/kg/day, interquartile range [IQR] 5.0 11.3 mL/kg/day) or as a continuous rate infusion (CRI; median dose 26mL/kg/day, IQR 24.0 48 mL/kg/day) In unadjusted analysis, HES administration was associated with increased risk of mortality (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.51 3.58, P 0.001) or AKI (OR 3.87, 95% CI 1.21 12.37, P 0.02) In an adjusted analysis after controlling for illness severity, admission type, and concurrent administration of blood products, HES administration remained an independent risk factor for the composite adverse outcome (OR 1.98, 95% CI 1.22 3.22, P 0.005) with a number needed to harm (NNH) 6 (95% CI 4 23) CONCLUSIONS HES therapy is associated with increased risk of an adverse outcome including death or AKI in dogs. A randomized controlled trial investigating the safety of HES therapy in canine patients is warranted.

title: Acute kidney injury in dogs

title: Urinary Neutrophil Gelatinase associated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicin induced Nephrotoxicity
abstract: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase associated lipocalin (NGAL) is a protein induced during kidney injury that may identify AKI earlier than traditional tests.  To evaluate urinary NGAL (uNGAL) and uNGAL to urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration.  Five purpose bred dogs.  Prospective study. Acute kidney injury, defined as a 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8 10 mg/kg SC q8h) Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery.  Acute kidney injury was diagnosed significantly earlier based on a 7 fold increase in UNCR compared to a 50% increase in serum creatinine concentration (day 8; range, 2 10 mg/dl vs day 16; range, 14 19 mg/dl; P .009) During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19) Conclusions and Clinical Importance The UNCR was early marker of gentamicin induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.

title: Adaptation of the Basso Beattie Bresnahan locomotor rating scale for use in a clinical model of spinal cord injury in dogs
abstract: Naturally occurring acute spinal cord injury (SCI) in pet dogs provides an important clinical animal model through which to confirm and extend findings from rodent studies; however, validated quantitative outcome measures for dogs are limited. NEW METHOD We adapted the Basso Beattie Bresnahan (BBB) scale for use in a clinical dog model of acute thoracolumbar SCI. Based on observation of normal dogs, modifications were made to account for species differences in locomotion. Assessments of paw and tail position, and trunk stability were modified to produce a 19 point scale suitable for use in dogs, termed the canine BBB scale (cBBB) Pet dogs with naturally occurring acute SCI were assigned cBBB scores at 3, 10 and 30days after laminectomy.  Scores assigned via the cBBB were stable across testing sessions in normal dogs but increased significantly between days 3 and 30 in SCI affected dogs (p=0.0003) The scale was highly responsive to changes in locomotor recovery over a 30day period, with a standardized response mean of 1.34. COMPARISON WITH EXISTING  Concurrent validity was good, with strong correlations observed between the cBBB and two other locomotor scales, the OSCIS (r=0.94; p<0.001) and the MFS (r=0.85; p<0.0001) cBBB scores inversely correlated with other assessments of recovery including mechanical sensory threshold (r= 0.68; p<0.0001) and coefficient of variation of stride length (r= 0.49; p<0.0001) CONCLUSIONS These results support the use of the cBBB to assess locomotor recovery in canine clinical translational models of SCI.

title: Mechanical and Thermal Sensory Testing in Normal Chondrodystrophoid Dogs and Dogs with Spinal Cord Injury caused by Thoracolumbar Intervertebral Disc Herniations
abstract: Intervertebral disc herniation is a common cause of spinal cord injury (SCI) causing paralysis and sensory loss. Little quantitative information is available on the loss and recovery of sensation in dogs with SCI.  To determine whether quantitative sensory testing (QST) can be used to establish thermal and mechanical sensory thresholds in chrondrodystrophoid dogs and compare thresholds among normal dogs and dogs with different grades of SCI. Animals Thirty three client owned chondrodystrophoid dogs: 15 normal and 18 SCI dogs.  Thermal testing was performed by placing a hot (49degC) and cold (5degC) probe on the dorsal metatarsus and mechanical thresholds were tested using calibrated forceps to apply force to the lateral digit. Stimuli were applied until acknowledged, and response rate, latency, and force applied to response were recorded. Test retest repeatability was determined by calculating intraclass correlation coefficients. Response rates were compared using logistic regression and thresholds were compared using Kaplan Meier Survival curves.  Testing was feasible with moderate repeatability. Thresholds and response rates were significantly different between normal and SCI dogs for all modalities (P .001) When dogs were grouped by their clinical grade, each grade was significantly different from normal dogs, and cold stimuli differentiated among all grades. Conclusion and clinical importance Sensory thresholds can be measured reliably in chondrodystrophoid dogs and are altered by SCI. The differences in sensation among neurologic grades indicate that these techniques can be used to further characterize recovery of SCI dogs.

title: Evaluation of autologous bone marrow derived mesenchymal stem cells on renal regeneration after experimentally induced acute kidney injury in dogs.
abstract: To evaluate the usefulness of autologous bone marrow derived mesenchymal stem cell (BM MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV) dogs immediately received saline (0.9% NaCl) solution (10 mL; n 3) or BM MSCs (1 x 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days 7 and 2; BM MSC tracking by MRI was performed on BM MSC treated dogs on days 14 and 4. After sample collection and BM MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays.  Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM MSC treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor a and transforming growth factor b were lower in the BM MSC treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM MSC treated dogs.  Results of this study suggested that autologous BM MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs.

title: Systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: Part 2.
abstract: To systematically evaluate the evidence reporting the diagnosis and management of meniscal injury in dogs with cranial cruciate ligament failure.  Systematic literature review.  Research questions relating to the accuracy of diagnostic techniques for meniscal injury and the effects of meniscal treatment were defined. An electronic database search of PubMed and CAB Abstracts was performed during March 2015. Data were extracted for study participants, design, intervention, outcome measures and results. Studies were evaluated using a validated instrument for assessing methodological quality and assigned a Quality Index score. A level of evidence was then assigned to each study.  Eighty nine studies were identified. The median Quality Index score was 14 out of a possible 26. Twenty seven studies were prospective case series, 31 retrospective case series, 16 animal research and 15 cadaveric studies. There were no class I or class II studies, 27 class III and 62 class IV studies.  Despite a large number of publications the quality of evidence was generally low. No one study or combination of studies provided high quality evidence to support one diagnostic or surgical intervention over another for meniscal injuries in dogs with cranial cruciate ligament failure.