Acute kidney injury in dogs: Etiology,clinical and clinicopathologic findings,prognostic markers,and outcome

BackgroundAcute kidney injury (AKI) is a common, potentially fatal condition.ObjectivesTo characterize the etiologies, clinical and clinicopathologic findings, hospitalization period, and outcome of dogs with AKI and to identify markers of negative prognosis.AnimalsTwo hundred forty‐nine client‐own dogs diagnosed with AKI and hospitalized at a veterinary teaching hospital.MethodsRetrospective study. Search of medical records for dogs with AKI.ResultsCommon clinical signs included lethargy (225/249, 90%), anorexia (206/249, 83%), and vomiting (168/249, 68%). Etiologies included ischemic/inflammatory (144/249, 58%), infectious (19/249, 8%), nephrotoxicosis (14/249, 6%), or other (13/249, 5%). Hospital‐acquired AKI was diagnosed in 9% (23/249) of the dogs. Median presentation and peak serum creatinine (sCr) concentrations were 4 mg/dL (range, 1.1‐37.9) and 4.6 mg/dL (range, 1.1‐43.1), respectively. Dogs were classified to AKI grades as follows: Grade I, 6 (2%), Grade II, 38 (15%), Grade III, 89 (36%), Grade IV, 77 (31%), and Grade V, 39 (16%). One hundred and sixty‐four (66%) dogs survived. There was a positive association between death and AKI grade (P = .009). The case fatality rate was higher among dogs with anuria compared with dogs without anuria (50% vs 28%, respectively; odds ratio [95% confidence interval]: 2.5 [1.39‐4.6]; P = .002). Forty‐seven (18.8%) dogs underwent hemodialysis, of which 60% survived.Conclusion and Clinical ImportanceTwo‐thirds of dogs with AKI survived. Hospital‐acquired AKI was common. The severity of AKI, as reflected by presence of anuria, AKI grade, and other body organs involvement, was associated with the outcome.     

Diagnostic accuracy of pre‐treatment biopsy for grading cutaneous mast cell tumours in dogs

Mast cell tumours (MCTs) are common tumours of the canine skin, and are estimated to represent up to 20% of all skin tumours in dogs. Tumour grade has a major impact on the incidence of local recurrence and metastatic potential. In addition to helping the clinician with surgical planning, knowledge of the tumour grade also assists in proper prognostication and client education. For pre‐treatment biopsies to be useful, there must exist a high level of correlation between the histopathological grade obtained from the pre‐treatment biopsy and the actual histopathological grade from the excisional biopsy. The aim of this study was to determine concordance of tumour grade between various biopsy techniques (wedge, punch, needle core) and the “gold standard” excisional biopsy method. We found an overall concordance rate of 96% based on the Patnaik grading system, and an overall concordance rate of 92% based on the Kiupel grading system. The accuracy of the various biopsy techniques (wedge, punch and needle core) when compared with excisional biopsy was 92%, 100% and 100%, respectively, based on the Patnaik grading system, and 90%, 95% and 100%, respectively, based on the Kiupel grading system. Of the cases with discordant results, the pre‐treatment biopsies tended to underestimate the grade of the tumour. Based on these results, we conclude that pre‐treatment biopsies are sufficiently accurate for differentiating low‐grade from high‐grade MCTs, regardless of biopsy technique or tumour location.     

The acute effects of a protein‐rich meal on the urinary corticoid:creatinine ratio in healthy dogs

The objective of this prospective crossover study was to investigate the effects of a high‐protein diet on canine urinary corticoid‐to‐creatinine ratio (UCCR). The hypothesis was that meal‐induced hypercortisolism is, as has been shown in humans, a predictable and consistent finding in healthy dogs. Eight clinic‐owned beagles were randomly assigned to one of two groups. The allocation to the groups defined the sequence of a protein‐enriched meal (meal A) or no meal on the first and second days, whereas on the third day all dogs again received an identical meal (meal B) to test reproducibility. Urinary corticoids were measured using a solid‐phase, competitive CLIA on unextracted urine. Contrary to our expectations, consistent incremental responses of the UCCR were not observed (meal A vs. no meal [anova ]: absolute increase, F = 2.546, p = 0.162; relative increase, F = 4.084, p = 0.09; AUC_(UCCR), F = 0.279, p = 0.616). Nevertheless, the robust increases in two dogs above 60% of baseline suggest that the collection of urine prior to feeding likely increases the specificity of the UCCR to discriminate between dogs with and without hypercortisolism.     

Proof-of-concept study: Evaluation of plasma and urinary electrolytes as markers of response to L-asparaginase therapy in dogs with high-grade lymphoma

Response to chemotherapy is one of the most important prognostic factors in dogs with lymphoma. The objective of this feasibility study was to evaluate if clinical responses to a specific cytotoxic agent (L-asparaginase) could be anticipated by measuring analyte concentrations in plasma and urine concentrations of lymphoma-bearing dogs. We hypothesized that potassium and phosphate concentrations in plasma and urine would be higher in dogs that completely responded to therapy. Plasma and urine samples of dogs with lymphoma were obtained before 12 and 24 hours after intramuscular L-asparaginase injections. Peripheral lymph node volumes were evaluated according to the Veterinary Cooperative Oncology Group standardized criteria. Plasma and urine electrolyte, calcium, phosphate, creatinine, urea, total protein, and albumin concentrations were measured, and the fractional excretions of each electrolyte were calculated. Statistical analyses compared complete vs partial responders using a linear regression model. Contrast analyses were also performed to differentiate the mean of each group, with adjustments made with the Benjamini-Hochberg procedure. Fourteen dogs were included, eight with complete responses, and six with partial responses. Plasma phosphate concentrations were significantly higher at 12 hours (P = .0003) and 24 hours (P = .009) after complete responses to therapy. This study demonstrates the potential use of plasma and urine analyte monitoring after chemotherapy induction. Plasma phosphate measurements represent a potential indicator of early responses to L-asparaginase therapy. Larger population studies are warranted to confirm these preliminary results.     

Diagnostic utility and cost‐effectiveness of reflex bacterial culture for the detection of urinary tract infection in dogs with low urine specific gravity

Background: Urinary tract infections (UTIs) may be subclinical or difficult to detect in dilute urine as sediment abnormalities may not be observed. In our laboratory, bacterial culture is automatically performed (reflex culture) on samples with urine specific gravity (USG)≤1.013 to increase the likelihood of detecting infection. The value of routine culture of dilute urine, however, has not been fully assessed. Objective: The purpose of this retrospective study was to evaluate the frequency of positive bacterial cultures and analyze the diagnostic utility and cost‐effectiveness of culture compared with routine sediment examination for detecting UTI in dilute urine specimens from dogs. Methods: Urinalysis and concurrent aerobic bacterial culture results were obtained from the electronic medical record system at the University of California–Davis Veterinary Medical Teaching Hospital for samples with USG≤1.013 analyzed from July 1998 through January 2005. Urine collection method, presence of leukocytes and bacteria, bacterial culture results, and clinical diagnosis were recorded. Cost‐effectiveness of reflex culture, based on low USG as the sole criterion, was evaluated. Results: Of 1264 urine specimens, 106 (8.4%) had positive bacterial cultures. Using culture as the gold standard, sediment evaluation had a diagnostic sensitivity of 58.5% and specificity of 98.3% (diagnostic accuracy 94.9%). An additional cost of $60 per patient was incurred, leading to average annual costs of $11,668 for reflex bacterial cultures of all samples with low USG, regardless of collection method. Within our study population, 10 urine samples needed to be cultured for each true positive result. Conclusions: The sensitivity of urine sediment evaluation is low for UTI in dilute urine samples; however, reflex bacterial culture does not appear to be cost‐effective in dogs with USG≤1.013 in the absence of active urine sediment or high clinical suspicion for UTI.     

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs

ObjectivesTo document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs.Study designExperimental, repeated measures, prospective study.AnimalsA group of six male adult Greyhound dogs.MethodsFollowing general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett’s adjustment, p < 0.05.ResultsStructural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1–25.9) ng mL^–1 NGAL (p = 0.002), 2.54 (1.64–3.43) mg mL^–1 CysC (p = 0.009) and 2043 (790–5458) U L^–1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein–creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage.Conclusions and clinical relevanceUrinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.     

Retrospective evaluation of COX‐2 expression,histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy

Limited veterinary literature is available regarding prognostic markers for canine renal cell carcinoma (CRCC). We retrospectively evaluated COX‐2 expression, histological and clinical features associated with prognosis of CRCC. Sixty‐four cases post‐nephrectomy were included, 54 had histopathological assessment and 30 had COX‐2 immunostaining performed. Eight dogs (13%) had metastatic disease at initial diagnosis. Twenty‐seven dogs (42%) received adjuvant therapy after nephrectomy. On univariate analysis, COX‐2 expression, mitotic index (MI), histologic type, vascular invasion, neoplastic invasiveness and metastasis at diagnosis were significantly associated with overall median survival time (MST). COX‐2 score (COX‐2 score > 3 MST 420 days versus 1176 days if COX‐2 score <3; P = 0.011) and MI (MI > 30 MST 120 days versus 540 days for MI < 30; P = 0.003) were the only variables associated with CRCC outcome on multivariate analysis. The addition of MI and COX‐2 immunostaining to standard histopathological evaluation would help predicting outcome in CRCC patients.