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Background: Urine cultures are frequently recommended to rule out infection as a postrenal cause of proteinuria., Objective: Identify characteristics associated with bacterial growth in urine in proteinuric dogs., Animals: Four hundred and fifty-one dogs admitted to a teaching hospital between January 2008 and January 2018 with urine protein-to-creatinine ratios (UPCs) >0.5., Methods: Retrospective study included dogs with a UPC, urinalysis, and quantitative urine culture (QUC) performed within a 72-hour period by searching electronic records. Dogs with recent antimicrobial therapy, urine collected by methods other than cystocentesis, or UPC ≤0.5 were excluded. Signalment, comorbidities, serum BUN and creatinine concentrations, urinalysis findings, and QUC results were recorded. The association between these characteristics and presence of bacterial growth in urine was assessed by univariable and multivariable analysis., Results: Thirty of four hundred fifty-one dogs (6.7%) had bacterial growth in urine. Of these, 18 (60.0%) had active urine sediment. Bacterial growth in urine was associated with pyuria (odd ratio [OR] 25.1, 95% confidence interval [CI] 7.9-79.6, P < .001), bacteriuria (OR 11.1, 95% CI 3.2-39.1, P < .001), and lower urinary tract disease (OR 6.7, 95% CI 1.9-23.0; P = .0028). If QUC was prompted based on these criteria, 8/451 (1.8%) of proteinuric dogs would have had undetected bacterial growth., Conclusions and Clinical Importance: The proportion of proteinuric dogs with both inactive urine sediment and bacterial growth in urine was low, suggesting that QUC might not be necessary in the evaluation of all proteinuric dogs. An active urine sediment or lower urinary tract disease should prompt QUC for proteinuric dogs., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Quantitative bacterial culture and susceptibility testing is the gold standard diagnostic for determining bacterial urinary tract infection. Transport of samples to external reference laboratories is common practice in veterinary medicine., Objective: To compare bacterial culture and susceptibility results from clinical urine samples when streak plate inoculation is performed immediately after sample collection versus after transport to a reference laboratory. To determine the clinical implications of discrepant culture results., Animals: One hundred and ninety-four canine and 45 feline urine samples that were submitted for urinalysis and urine culture and susceptibility testing., Methods: This was a prospective, cross-sectional study. Streak plate inoculations were performed on urine samples immediately after collection and also after transport to a reference laboratory. Samples were stored in plain sterile tubes and refrigerated up to 24 hours before transport. Culture results were compared, and discordant results were evaluated for clinical relevance. Signalment, comorbidities, lower urinary tract signs, and antimicrobial history were recorded., Results: Kappa coefficient for agreement between plating methods was 0.884. Twenty-two (71%) of 31 discrepant results were determined to have no clinical impact. Though 35% of clean midstream samples had discrepant culture results, only 8% of these had clinical impact. Conversely, 8.6% from cystocentesis were discrepant, but 41% of these had clinical impact., Conclusions and Clinical Importance: Provided urine samples are stored and transported appropriately, the immediate preplating of urine for culture and susceptibility testing is unnecessary in the majority of cases. Despite more discrepancies in plating methods for midstream samples, the minority were of clinical importance., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: We aimed to identify a simple test for excessive calciuresis and predict calcium oxalate (CaOx) disease in Miniature Schnauzers. We investigated the impact of postprandial time on the urine calcium to creatinine ratio (UCa/Cr) in male dogs of this breed, with the goal of improving the utility of the UCa/Cr., Hypotheses: (1) Significant differences will exist in preprandial and postprandial UCa/Cr between CaOx urolith-forming and control Schnauzers. (2) The UCa/Cr will increase significantly from the first morning baseline at ≥1 postprandial time point(s) in both control and CaOx urolith-forming dogs. (3) Biochemical abnormalities and other variables may be associated with urolith status., Animals: Twenty-four male Miniature Schnauzer dogs, consisting of 9 with (urolith formers) and 15 without (controls) CaOx uroliths., Methods: Urine was collected before and 1, 2, 4, and 8 hours after feeding a standardized diet. Receiver operator characteristic curve analysis was performed to identify the UCa/Cr cutoff that most accurately differentiates dogs based on urolith status., Results: Urolith formers had significantly higher mean UCa/Cr over the course of 8 hours. The postprandial change in UCa/Cr was not significant at any time point between or within groups. The cutoff UCa/Cr value of 0.06 had a specificity of 93% (95% confidence interval [CI], 80%-100%) and a sensitivity of 56% (95% CI, 21%-86%) for identifying CaOx urolithiasis., Conclusions and Clinical Importance: Urolith-forming male Miniature Schnauzers have excessive calciuresis, and the postprandial sampling time up to 8 hours is not critical. This simple urine measurement has potential as a marker of CaOx disease., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of α-amanitin (α-AMA) or γ-AMA, and 100 ng/mL of β-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography-mass spectrometry (LC-MS) methods.

Background: Urine neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs., Objectives: To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis., Animals: Dogs with AKI (n = 76) and healthy controls (n = 10)., Methods: Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume-responsive (VR-) AKI vs. intrinsic (I-) AKI based on IRIS criteria; VR-AKI and I-AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P < .05., Results: Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR-AKI and I-AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I-AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified., Conclusions and Clinical Importance: Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I-AKI and VR-AKI also suggests the presence of tubular damage in transient AKI. Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Neutrophil gelatinase-associated lipocalin (NGAL) is used as an early biomarker of renal injury in people. In dogs, increases in urinary NGAL (uNGAL) precede increases in serum creatinine (sCr) in experimental and clinical evaluations of acute kidney injury (AKI) and chronic kidney disease. This study compared uNGAL in two subsets of dogs with AKI and their respective controls. One set included dogs with snake-envenomation at risk for or presenting with International Renal Interest Society (IRIS) grade I AKI; the other group included dogs with AKI, where renal injury was the result of various causes, and IRIS grade was ≥II. Additionally, this study evaluated haemoglobin (Hb) interference during NGAL analysis in Hb spiked urine and plasma from healthy dogs. In both AKI groups, uNGAL was significantly higher than in matched healthy control dogs (P<0.01). Moreover, uNGAL was significantly higher in dogs with IRIS grade ≥II AKI than in dogs at risk of IRIS grade I AKI (P=0.04). In dogs at risk of IRIS grade I AKI, there were no significant differences in uNGAL and uNGAL/uCr between dogs bitten by cytotoxic or neurotoxic snakes (P=0.44). Additionally, Hb did not interfere with the canine NGAL immunoassay. In conclusion, this study confirms the value of uNGAL as a biomarker for early renal damage: uNGAL was significantly increased in dogs with snake-envenomation at risk for or presenting with IRIS grade I AKI, which could be left undiagnosed if evaluated with the traditional renal biomarker sCr. In addition, Hb did not interfere with NGAL measurement in dogs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRD K ), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRD K in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored. Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRD K was suggested by the association between LVPWDN and survival., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Acute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia. Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry., Results: In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses., Conclusions: It was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-β (transforming growth factor β) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury.

Urinary tract infections (UTI) occur commonly in dogs, and gram-negative enteric bacteria are the most prevalent pathogens. Clinical parameters, urinalysis, and urine culture and sensitivity results were retrieved from the medical records of 208 dogs with positive urine cultures over a 3 yr period at the Louisiana State University Veterinary Teaching Hospital. Several groups were defined including dogs presented for primary care versus referred cases; simple UTI, complicated UTI, and pyelonephritis; dogs pretreated with antimicrobials; and dogs having an indwelling catheter in place prior to sampling. Nearly 80% of dogs had complicated UTI. Of all dogs, 70% had no documented clinical signs of lower urinary tract disease (LUTD), with 68% of them showing hematuria and/or pyuria. Based on clinical signs or urinalysis, 19% of all dogs had no evidence of lower UTI. In dogs without LUTD signs the most common comorbidities were immunosuppressive treatment and severely restricted mobility (23%). Chronic recurring UTI were present in 19% of dogs with LUTD signs. Distribution of bacterial species was comparable with the existing literature and not significantly different between clinical subgroups. Isolates from dogs pretreated with antimicrobials showed decreased susceptibility to enrofloxacin. The prevalence of multidrug-resistant Escherichia coli and Staphylococcus spp. was moderate (29%).

Individual variability is evident in behavior and physiology of animals. Determining whether behavior at intake may predict subsequent illness in the animal shelter may influence the management of dogs housed at animal shelters and reduce overall disease. While normally associated with mild disease and low mortality rates, respiratory disease nevertheless poses significant challenges to the management of dogs in the stressful environment of animal shelters due to its highly infectious nature. Therefore, the aim of the study was to explore whether behavior at intake can predict subsequent occurrence and progression of upper respiratory disease in dogs at animal shelters. In a correlational study, 84 dogs were assessed throughout their stay at a city animal shelter. The dogs were subjected to a behavioral assessment, 1 min in-kennel behavioral observations across two observation periods, and the collection of urinary cortisol:creatinine (C:C) ratio. The occurrence and progression of upper respiratory disease was monitored through repeated clinical exams (rectal temperature and the occurrence of nasal and ocular discharge, and presence of coughing and sneezing). A basic PLS Path regression model revealed that time in the shelter (estimate = .53, p < .001), and sociability (estimate = .24, p < .001) and curiosity scores (estimate = .09, p = .026) were associated with increased illness. Activity and anxiety scores, however, were not associated with illness. Urinary C:C, taken on the first full day, did not predict subsequent illness when accounting for time. Limitations included attrition of dogs, a small percentage receiving vaccinations, and continuous and non-systematic rotation of dogs in the kennels. Understanding if behavior can predict subsequent illness may improve shelter management practices, and in turn, result in improved live-release outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate effects of the addition of glucose to dog and cat urine on urine specific gravity (USG) and determine whether glucosuria affects assessment of renal concentrating ability., Sample: Urine samples from 102 dogs and 59 cats., Procedures: Urine for each species was pooled to create samples with various USGs. Glucose was added to an aliquot of each USG pool (final concentration, 2,400 mg/dL), and serial dilutions of the glucose-containing aliquot were created for each pool. The USG then was measured in all samples. The difference in USG attributable to addition of glucose was calculated by subtracting the USG of the unaltered sample from the USG of the sample after the addition of glucose. The relationship between the difference in USG and the USG of the unaltered, undiluted sample was evaluated by the use of linear regression analysis., Results: Addition of glucose to urine samples increased the USG. There was a significant relationship between USG of the undiluted sample and the difference in USG when glucose was added to obtain concentrations of 300, 600, 1,200, and 2,400 mg/dL in canine urine and concentrations of 600, 1,200, and 2,400 mg/dL in feline urine. The more concentrated the urine before the addition of glucose, the less change there was in the USG. Changes in USG attributable to addition of glucose were not clinically important., Conclusions and Clinical Relevance: Substantial glucosuria resulted in minimal alterations in specific gravity of canine and feline urine samples. Thus, USG can be used to assess renal concentrating ability even in samples with glucosuria.

In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle-invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient-derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA-sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two-dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle-invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218 H-AAEILAATPAAVQLR-OH 232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

Urinary and blood biomarkers for diagnosis of acute kidney injury (AKI) in hospitalised dogs were evalueted. This prospective study included 97 dogs, classified according to the International Renal Interest Society classification into no AKI and AKI grade 1 (48-hour increase in serum creatinine≥0.3 mg/dl and/or urinary production <1 ml/kg/hour for at least six hours). A total of 62 of 97 dogs (64 per cent) were classified as AKI 1. A statistically significant difference was found between no AKI and AKI 1 in urine protein to creatinine ratio, urinary γ-glutamyl transferase (uGGT) and uGGT/cu (P<0.0001). Thirteen of 97 dogs (13.4 per cent) that developed increased creatinine and change in AKI grade showed high mortality (n=9/13; 69.2 per cent). The receiver operating characteristic (ROC) curve analysis of uGGT/cu index as a marker for AKI grade 1 had an area under the ROC curve of 0.78; optimal cut-off point was 57.50 u/g, with sensitivity and specificity of 75.4 per cent and 75.6 per cent, respectively. Overall intensive care unit mortality was 23.7 per cent (23/97), 13.4 per cent (13/97) of which died during hospitalisation and 10.3 per cent (10/97) within 28 days after discharge. uGGT is an acceptable marker for distinguishing between AKI 1 and no AKI., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic kidney disease (CKD) is clinically important in canine medicine. Current diagnostic tools lack sensitivity for detection of subclinical CKD. The aim of the present study was to evaluate urinary peptidome analysis for diagnosis of CKD in dogs. Capillary electrophoresis coupled to mass spectrometry analysis demonstrated presence of approximately 5400 peptides in dog urine. Comparison of urinary peptide abundance of dogs with and without CKD led to the identification of 133 differentially excreted peptides (adjusted P for each peptide <0.05). Sequence information was obtained for 35 of these peptides. This 35 peptide subset and the total group of 133 peptides were used to construct two predictive models of CKD which were subsequently validated by researchers masked to results in an independent cohort of 20 dogs. Both models diagnosed CKD with an area under the receiver operating characteristic (ROC) curve of 0.88 (95% confidence intervals [CI], 0.72-1.0). Most differentially excreted peptides represented fragments of collagen I, indicating possible association with fibrotic processes in CKD (similar to the equivalent human urinary peptide CKD model, CKD273). This first study of the urinary peptidome in dogs identified peptides that were associated with presence of CKD. Future studies are needed to validate the utility of this model for diagnosis and prediction of progression of canine CKD in a clinical setting., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in-clinic laboratory tests. No independent, evidence-based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe., (© 2019 American Society for Veterinary Clinical Pathology.)

Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography-quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Lawrence, Steiner, Suchodolski, and Lidbury are employed by the Gastrointestinal Laboratory at Texas A&M University that provides intestinal function and hepatic function tests on a fee-for-service basis. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Dry reagent strip evaluation of urine is a standard screening and diagnostic test used to assess overall health and help detect or rule out specific disease conditions. A commercial at-home urinalysis reagent strip kit using a smartphone app to evaluate free-catch urine is being marketed directly to dog and cat owners. We compared agreement between simultaneous urinalysis using the commercial kit and standard reference methods in 48 canine urines submitted to our referral laboratory. Agreement was defined by analyte based on clinical impact. Sensitivity, specificity, and Cohen's kappa evaluated categorical data, and a paired t test was used for continuous variables (significance P < .05). The commercial kit had ≥1 disagreement with the reference method per sample and produced results if the test strip was absent or reversed. Specific gravity and pH concurred with the reference method in only 31% ( P < .011) and 27% ( P < .001) of cases, respectively. The sensitivity was low for all analytes except ketones, which had 77% false positives. False-positive nitrites and leukocytes were also frequent (36 and 19%, respectively). False negatives for blood (27%), nitrites (38%), and protein (54%) were common. This kit is inaccurate; its use for clinical decisions is not recommended.

Background: There are abnormalities in vitamin D metabolism in people with calcium nephrolithiasis, but limited data are available on vitamin D status in dogs with calcium oxalate (CaOx) urolithiasis., Objective: To compare serum concentrations of vitamin D metabolites in dogs with and without hypercalciuric CaOx urolithiasis., Animals: Thirty-eight dogs with (n = 19) and without (n = 19) a history of CaOx urolithiasis and hypercalciuria., Methods: Retrospective cross-sectional study. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH) 2 D], and 24,25-dihydroxyvitamin D [24,25(OH) 2 D] were measured. The ratios of 25(OH)D/24,25(OH) 2 D and 1,25(OH) 2 D/25(OH)D were compared between cases and controls., Results: There were no significant differences between cases and controls when comparing 25(OH)D, 24,25(OH) 2 D, 1,25(OH) 2 D, or 1,25(OH) 2 D/25(OH)D. Cases had higher 25(OH)D/24,25(OH) 2 D (median = 1.40, range = 0.98-1.58) compared to controls (median = 1.16, range = 0.92-2.75; P = .01). There was overlap in the ranges for 25(OH)D/24,25(OH) 2 D between cases and controls, but 6 cases (32%) had ratios above the control dog range. There was a moderate positive correlation between the ratio of 25(OH)D/24,25(OH) 2 D and urinary calcium-to-creatinine ratios (r = 0.40, 95% confidence interval = 0.10-0.64; P = .01)., Conclusions and Clinical Importance: These data suggest that decreased conversion of 25(OH)D to 24,25(OH) 2 D occurs in a subset of dogs with CaOx urolithiasis. Abnormalities in vitamin D metabolism might contribute to stone risk in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Oxidative stress is associated with a diverse group of liver disorders across species., Objectives: Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8-isoprostanes/creatinine (F 2 -IsoPs/Cr) concentrations, correlate with liver GSH., Animals: Thirty-four client-owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs., Methods: Prospective, observational cross-sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F 2 -IsoPs/Cr was measured by gas chromatography/mass spectrometry., Results: All dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F 2 -IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F 2 -IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001)., Conclusions and Clinical Importance: Erythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Cytologic evaluation of the urinary tract can be diagnostically rewarding in cases of renomegaly or when discrete kidney or bladder masses are identified. Cytology can often help to distinguish between cystic, inflammatory, and neoplastic disorders. Various types of cystic and benign urinary tract lesions, diseases associated with urinary tract inflammation, and the cytologic differences between primary and metastatic neoplasms of the kidney and bladder are described. Basic sampling techniques for urinary tract cytology are also discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Studies have shown an increased prevalence of positive urine culture (PUC) in cats with chronic kidney disease (CKD); no information is available in dogs., Objectives: To document the PUC frequency in a cohort of dogs with CKD, determine risk factors for PUC, and identify associations between clinicopathologic data and PUC., Animals: Two hundred one client-owned dogs with CKD., Methods: Retrospective, observational study. Dogs recruited from 2 veterinary teaching hospitals were included if they were diagnosed with CKD and had a culture performed on urine collected by cystocentesis. The PUC frequency was calculated, multivariate analysis was performed to identify risk factors, and associations with clinicopathologic data were investigated., Results: Sixty-five dogs (32%) with CKD had PUC, including 8 (28%) in International Renal Interest Society (IRIS) stage 1; only 8% showed signs of a urinary tract infection. Escherichia coli was the most common isolate (67%). A PUC was more likely in females (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.67-6.37; P < .001) than males and in dogs with isosthenuria (OR, 2.48; 95% CI, 1.24-5.03; P = .01) than in dogs with urine-specific gravity 1.013-1.024. A positive leukocyte esterase test and microorganisms found by urine sediment analysis were significantly associated with PUC (both P < .001)., Conclusions and Clinical Importance: Dogs with CKD, even IRIS stage 1, have a high frequency of PUC and most cases are asymptomatic. A urine culture could be considered in the routine evaluation of dogs with CKD, but the clinical relevance of a PUC remains unknown and needs further evaluation., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

A complete urinalysis is an essential diagnostic test to perform in veterinary patients. When interpreted in the context of a patient's clinical history, physical examination findings, and other diagnostic test results, a urine specific gravity, chemical analysis (often via semiquantitative dipstrip testing), and sediment examination are vital to detect both renal and nonrenal disorders. In this article, we describe the usefulness of each component of a urinalysis, the significance of and how to interpret results, and common causes of false-negative and false-positive results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Candida urinary tract infections occur in both dogs in cats but there is limited data about risk factors., Objective: To identify risk factors for candiduria in dogs in cats., Animals: Eighteen dogs and 8 cats with candiduria., Methods: A retrospective case-control study, using univariate exact logistic regression. Medical records were searched for a diagnosis of Candida and animals with culture-confirmed candiduria were enrolled. Controls had bacterial cystitis (dogs and cats) or cutaneous Malassezia infection (dogs only)., Results: Administration of antibacterial drugs in the 30 days before diagnosis was associated with candiduria in dogs compared to controls with bacterial cystitis (OR 14.5; 95% CI 3.1-66.9) or with Malassezia infection (OR 26.4; 95% CI 3.4-206.7). Antecedent antibacterial drug administration was associated with candiduria in cats (OR 15.7; 95% CI 1.9-132.3). Immunosuppression was associated with candiduria in dogs when compared to controls with Malassezia infection (OR 4.2, 95% CI 1.4-12.8), but not significantly when compared to dogs with bacterial cystitis (OR 2.7, 95% CI 0.9-8.0). Lower urinary tract diseases other than infection were associated with candiduria in cats (OR 6.7, 95% CI 1.6-27.9), but not significantly in dogs (OR 2.5, 95% CI 0.7-8.7). Neither diabetes mellitus nor history of hospitalization was significantly associated with candiduria in either species., Conclusions and Clinical Importance: The recent administration of antibacterial drug therapy is a potential risk factor for development of candiduria in dogs and cats. Judicious use of antibacterial drugs might help to prevent candiduria., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Chemokine (C-C motif) ligand 2 (CCL2) is a chemotactic cytokine recruiting monocytes, releasing growth factors and promoting adhesion in vascular endothelium. Elevated serum and urinary CCL2 levels and expression of its receptor (CCR2) have been associated with tumorigenesis in human urinary malignancies. CCL2 implication has not been investigated in canine urothelial carcinoma. The aim of this study was to evaluate CCL2 serum and urine levels (measured by ELISA) in dogs with urothelial carcinoma or non-neoplastic urinary tract disease. CCL2 serum and urine levels were significantly higher in diseased dogs compared with healthy dogs (P < 0.001). Dogs with carcinoma had significantly higher serum and urine CCL2 levels (P = 0.001) than healthy dogs. Dogs with metastases showed significantly lower serum and urine CCL2 levels compared with the non-metastasised tumour group (P = 0.007). CCL2 as a diagnostic marker for urothelial carcinoma held a sensitivity of 95.2% and a specificity of 38.2% in the urine. As a staging marker, sensitivity was 85.7% and specificity was 57.1% with a positive predictive value of 75.7% and a negative predictive value of 71.9%. Further investigation is needed to define the role of CCL2 as a prognostic marker in canine urothelial carcinoma., (© 2018 John Wiley & Sons Ltd.)

Aims: To determine the effect of contamination of urine with 0-5% blood, varying in haematocrit and protein concentrations, on the urine protein to creatinine ratio (UPC) in dogs, and to determine whether the colour of urine can be used to aid interpretation of UPC results., Methods: Urine samples were collected by free catch from 18 dogs, all of which had UPC <0.2. Venous blood samples were also collected from each dog, and the blood from each dog was added to its own urine to produce serial concentrations of 0.125-5% blood. The colour of each urine sample was recorded by two observers scoring them as either yellow, peach, orange, orange/red or red. Protein and creatinine concentrations were determined, and dipstick analysis and sediment examination was carried out on each sample. Based on colour and dipstick analysis, samples were categorised as either having microscopic, macroscopic or gross haematuria. A linear mixed model was used to examine the effect of blood contamination on UPC., Results: The uncontaminated urine of all 18 dogs had a UPC <0.2. Adding blood to the urine samples resulted in an increase in UPC at all contamination concentrations compared to the non-contaminated urine (p<0.001). None of the 54 samples with microscopic haematuria had UPC >0.5. For 108 samples with macroscopic haematuria the UPC was >0.5 in 21 samples (19.4 (95% CI=13.1-27.9)%), and for 54 samples with gross haematuria 39 (72 (CI=59.1-82.4)%) had a UPC >0.5. No samples had a UPC >2.0 unless the blood contamination was 5% and only 3/18 (17%) samples at this blood contamination concentration had a UPC >2.0., Conclusions and Clinical Relevance: This study showed that while blood contamination of ≥0.125% does increase the UPC, if the urine remains yellow (microscopic haematuria), then there is negligible chance that a UPC >0.5 will be solely due to the added blood. In that scenario, attributing the proteinuria present to the haematuria in the sample would be inappropriate. However blood contamination that results in discolouration of the urine sample from yellow (indicating macroscopic or gross haematuria) could increase the UPC above the abnormal range and would need to be considered as a differential for the proteinuria. Thus knowledge of urine colour, even if limited to simple colour scores (yellow, discoloured, red) could be utilised to aid interpretation of the UPC in samples with haematuria.

Background: Active kidney injury may play a role in chronic kidney disease (CKD) progression in dogs. Neutrophil gelatinase-associated lipocalin (NGAL), a novel tubular kidney injury biomarker, may help differentiate progressive CKD from stable CKD in dogs., Objectives: To determine if urinary NGAL : creatinine ratio (UNCR) differentiates stable and progressive CKD in dogs. We hypothesized that UNCR would be higher in dogs with progressive CKD versus stable CKD., Animals: Twenty-one healthy control dogs, 22 with prerenal azotemia, 19 with stable CKD, 30 with progressive CKD, and 27 with acute kidney injury (AKI)., Methods: Prospective study. Azotemic (serum creatinine concentration >1.6 mg/dL) dogs or nonazotemic AKI dogs were enrolled and classified into 4 groups: (1) prerenal azotemia, (2) stable CKD, (3) progressive CKD, and (4) AKI. Urinary NGAL was measured by ELISA and UNCR compared among groups. Urine protein : creatinine ratio (UPC) in dogs with stable and progressive CKD was compared to UNCR for differentiating CKD groups., Results: UNCR was significantly higher in dogs with progressive CKD than stable CKD. UNCR of the prerenal azotemia group was significantly lower than that of the progressive CKD and AKI groups. No significant difference was found in UNCR between stable CKD and prerenal azotemia groups. ROC curve analysis of UNCR for differentiating progressive CKD from stable CKD resulted in an AUC of 0.816 (95% confidence interval [CI], 0.673-0.959), greater than that of UPC (0.696; 95% CI, 0.529-0.863)., Conclusions and Clinical Importance: Urinary NGAL could be helpful to predict the risk of progression in dogs with CKD., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Inherited skeletal disorders affect both humans and animals. In the current study, we have performed series of clinical, pathological and genetic examinations to characterize a previously unreported skeletal disease in the Karelian Bear Dog (KBD) breed. The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties. Exome sequencing of one affected dog revealed a homozygous missense variant (c.1301T > G; p.V434G) in the tissue non-specific alkaline phosphatase gene, ALPL. The identified recessive variant showed full segregation with the disease in a cohort of 509 KBDs with a carrier frequency of 0.17 and was absent from 303 dogs from control breeds. In humans, recessive and dominant ALPL mutations cause hypophosphatasia (HPP), a metabolic bone disease with highly heterogeneous clinical manifestations, ranging from lethal perinatal hypomineralization to a relatively mild dental disease. Our study reports the first naturally occurring HPP in animals, resembling the human infantile form. The canine HPP model may serve as a preclinical model while a genetic test will assist in breeding programs.

In dogs with leptospirosis, doxycycline therapy is recommended as the preferred therapy for its ability to eliminate the organism from all tissues, including the renal tubules. Elimination of organisms from the renal tubules terminates leptospiruria and prevents transmission of the organism. This report describes the discovery of persistent leptospiruria in the face of therapy with doxycycline in four dogs and enrofloxacin in one dog. Leptospiruria was confirmed by polymerase chain reaction testing for pathogenic leptospires in all five dogs. In two dogs, leptospiruria resolved after a change in therapy to enrofloxacin. In three dogs, doxycycline and/or enrofloxacin were ineffective at eliminating leptospiruria, which then resolved after therapy with clarithromycin. Pet owners could be at risk as persistent leptospiruria poses a potential zoonotic risk. The potential reasons for persistent leptospiruria as demonstrated by polymerase chain reaction testing are discussed.

Background: Proteinuria is a marker of chronic kidney disease in dogs and a risk factor for increased morbidity and death. Predictive models using the results of readily available screening tests could foster early recognition., Objective: To determine whether urine specific gravity (USG) and semiquantitative category of dipstick protein can be used to predict urinary protein-to-creatinine ratio (UP : C) and to examine the effect of urine culture results on UP : C in dogs., Animals: Three hundred ninety-four dogs (482 visits) presented to a university Community Practice Clinic or Veterinary Teaching Hospital between January 2011 and November 2015., Methods: Retrospective study. Medical records were searched to identify dogs for which urinalysis, UP : C measurement, and urine culture testing were performed during a single hospital visit. Urine specific gravity, UP : C, dipstick protein concentration, and findings of urine sediment analysis and urine culture were recorded. Regression or Spearman correlation analysis was used to test for relationships between UP : C and USG within dipstick categories and between UP : C and bacterial colony-forming units per milliliter, respectively. Cohen's kappa test was used to evaluate agreement between urine culture and UP : C testing., Results: There were significant (P < .05) weak negative correlations (R 2 range, 0.14-0.37) between UP : C and USG for all nonnegative urine protein dipstick categories. The presence of a positive urine culture did not agree with the presence of abnormal UP : C (κ = -0.06)., Conclusions and Clinical Importance: Within dipstick protein categories, UP : C cannot be accurately predicted from USG. Repeating UP : C measurement after resolution of urinary tract infection is advisable., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Dogs with naturally occurring canine parvovirus (CPV) infection are at risk of developing acute kidney injury (AKI) due to several factors, including severe dehydration, hypotension and sepsis. Serum creatinine (sCr) and serum urea are insensitive markers for the assessment of early kidney injury. Therefore, the aim of this study was to investigate potential kidney injury in dogs with CPV infection using both routine renal functional parameters and several kidney injury biomarkers. Twenty-two dogs with CPV infection were prospectively enrolled and compared with eight clinically healthy control dogs. Urinary immunoglobulin G (uIgG) and C-reactive protein (uCRP) were measured to document glomerular injury, whereas urinary retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL) served as markers for tubular injury. These biomarkers were compared to routine renal functional parameters, including sCr, serum urea, urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). Dogs with CPV infection had significantly higher concentrations of uIgG, uCRP, uRBP and uNGAL compared to healthy dogs. In contrast, sCr was significantly lower in dogs with CPV infection compared to controls, while serum urea was not significantly different. UPC and USG were both significantly higher in CPV-infected dogs. This study demonstrated that dogs with CPV infection had evidence of AKI, which remained undetected by the routine functional markers sCr and serum urea, but was revealed by UPC, uIgG, uCRP, uRBP and uNGAL. These results emphasize the added value of novel urinary kidney injury biomarkers to detect canine patients at risk of developing AKI., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In dogs, spontaneous Cushing's syndrome is most often pituitary-dependent and caused by hypersecretion of adrenocorticotropic hormone (ACTH), resulting in increased adrenocortical glucocorticoid secretion similar to horses. In horses with Cushing's syndrome (or pituitary pars intermedia dysfunction [PPID]) a thyrotropin-releasing hormone (TRH) stimulation test can be used for diagnosis, as TRH administration results in increased circulating ACTH and cortisol concentrations in affected horses., Objective: The aim of this study was to investigate the effect of TRH administration on the circulating ACTH and cortisol concentrations in dogs with pituitary-dependent hypercortisolism (PDH)., Methods: Ten clinically normal control dogs and 10 dogs with PDH, all client owned, underwent a TRH stimulation test with measurement of plasma concentrations of ACTH and cortisol, before and after intravenous administration of 10 μg TRH/kg bodyweight., Results: Plasma ACTH concentration did not rise significantly after TRH stimulation, neither in PDH dogs nor in clinically normal dogs. In contrast, the plasma cortisol concentration did increase significantly after TRH stimulation in both groups (p = .003 in PDH and p < .001 in control). Immunohistochemistry of normal adrenal glands demonstrated the presence of TRH receptors in the whole adrenal cortex., Conclusions: The results of this study demonstrate that the TRH stimulation test should be rejected as a tool to diagnose PDH in dogs. The observed TRH-induced increase in plasma cortisol concentration without a significant rise in plasma ACTH concentration may be explained by a direct effect of TRH on adrenocortical cells mediated by adrenocortical TRH receptors.

A 1 yr old intact male miniature dachshund presented for posturing to urinate without voiding and nocturia. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure caudal to the urinary bladder. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy with an attempt to remove the cyst. Twelve weeks later, the dog returned with recurring clinical signs, and the cyst was found to have returned back to its original size. A second intact male miniature dachshund presented at 7 mo of age for stranguria. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure on rectal palpation, much like the first dog. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy. An attempt was made to close communication between the prostate and cyst. The dog re-presented 3 wk later for recurrence of clinical signs, and the prostatic cyst was found to have increased in size. Both dogs were euthanized because of recurrence of clinical signs. This report describes the presence of prostatic cysts in two young dogs with congenital abnormalities of the genital and reproductive tracts and the similarities seen in human boys diagnosed with prostatic utricles.

Urine dipstick results may vary between operators/methods. The magnitude of variation across the veterinary field is currently unknown. The aim of this study was to compare the precision of urine dipstick results between standard direct visual and automated reading methods when performed by several operators. Urine samples were pooled and divided into three aliquots: one plain, one with glucose and one with serum. Final year students, veterinary surgeons and veterinary nurses, blinded to each sample, were then asked to perform dipstick analysis with direct visualisation and an automated analyser, and their technique was observed. A subsequent session was undertaken with samples which had pH titrated to achieve an acidic, neutral or alkaline value. Sixty-four veterinary students, 20 veterinary surgeons and seven veterinary nurses performed the first (n=61) or second (n=30) part of the study. Precision was greater using the automated reader. The most common observed technique errors were: lack of sample mixing, for both visual and automated methods, and not timing readings as per manufacturer instructions when performing visual analysis. This study suggests that in an environment with multiple operators, as is the case in veterinary teaching or large private hospitals, automated urine dipstick reading improves precision of results., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Preanalytic protein adsorption to polymer and glass container surfaces may decrease urine protein concentration measurements and urine protein: creatinine ratios (UPC)., Hypothesis/objectives: Urine stored in PC or glass containers will have lower UPC than urine stored in HP containers. The specific objective was to determine whether clinically relevant differences in UPC would be detected after storage in glass, PC, or HP containers using common storage times and temperatures., Animals: Twelve client-owned dogs with proteinuria., Methods: Prospective, nonmasked study, divided into 2 phases. The first phase was a pilot study involving multiple (n = 5) measurements at each storage condition using 24-hours urine samples from 2 dogs with persistent renal proteinuria of different magnitude. The second phase used urine samples from 10 dogs with proteinuria of variable magnitude. Sample aliquots were stored in HP, PC, and glass containers at 24°C for 4 hours, 4°C for 12 hours, and -20°C for 72 hours. The UPC of each was measured after storage and compared with baseline., Results: Statistically significant but clinically irrelevant differences were found in phase 1. In phase 2, storage conditions did not affect urinary protein or creatinine concentrations or UPC., Conclusions and Clinical Importance: Collection and storage of canine urine samples in clean HP, PC, or glass containers at 24°C for 4 hours, 4°C for 12 hours, or -20°C for 72 hours is unlikely to result in clinically relevant decreases in measured UPC values., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Canine babesiosis is a tick-borne disease caused by the haemoprotozoan parasites of the genus Babesia. The aim of this study was to assess renal dysfunction in dogs with babesiosis caused by B. canis, using serum and urinary markers for both glomerular and tubular dysfunction. Assays previously not validated for use in canine samples were validated and the potential interference of haemoglobin, lipids and bilirubin with these analyses was additionally considered. In this study 42 dogs naturally infected with B. canis and 14 healthy dogs were included. Dogs with babesiosis were divided into 3 groups: group A consisted of 9 non-azotemic dogs with normal urine protein to creatinine ratio (UPC < 0.5), group B of 27 non-azotemic dogs with UPC > 0.5 and group C of 6 azotemic dogs with UPC > 2. The concentrations of urinary immunoglobin G (IgG), retinol binding protein (RBP), uromodulin, kidney injury molecule - 1 (KIM-1), and serum symmetric dimethylarginine were measured by ELISA assays, while urinary albumin and N-acetyl-b-D-glucosaminidase (NAG) were evaluated by an immunoturbidimetric and enzymatic colorimetric assay, respectively. Urinary markers were normalized to urine creatinine concentration. All tested markers, with exception of uromodulin, showed significant differences between dogs with babesiosis and healthy dogs, and also showed strong or very strong positive correlation with UPC. Increases of urinary albumin and IgG suggested glomerular damage, and increases of KIM-1, RBP and NAG proximal tubular damage in dogs with babesiosis. They demonstrated clear advantages compared to conventional parameters by showing earlier changes in detecting renal damage., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs., Objectives: We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD., Methods: We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined., Results: Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage., Conclusions and Clinical Importance: Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD., (© 2018 The Authors. Veterinary Clinical Pathology Published by John Wiley & Sons Ltd.)

Bloodstream infections are a significant cause of morbidity and mortality in critically ill dogs, but due to cost and difficulties in sample acquisition, blood cultures are infrequently obtained. In ill dogs, urine cultures may be recommended as surrogates for blood cultures. In order to determine the outcome agreement between parallel urine and blood cultures, we retrospectively analyzed parallel blood and urine specimens submitted for culture from dogs at the NC State Veterinary Hospital between 2011 and 2016. Positive cultures were reported from 15% of the submitted blood specimens and 23% of the submitted urine specimens. A total of 295 urine and blood samples were submitted in parallel, with positive growth demonstrated in 14 concordant and five discordant pairs. A kappa statistic comparing blood and urine culture outcomes was 0.266 (fair) when all parallel growth was included, including concordant and discordant results, and 0.170 (poor) when restricted to parallel concordant growth. The sensitivity of urine to reflect concordant bloodstream bacterial organisms was 30%, with a specificity of 87%. The positive and negative predictive values were 30% and 88%, respectively. Of dogs with both specimens positive on bacterial culture, 7 of 7 (100%) with suspected urogenital infection sources were concordant. All dogs with discordant bloodstream and urinary infections were immunosuppressed. Urinary coagulase-positive Staphylococcus isolates were most likely to be concordant with bloodstream infections. In conclusion, we found that urine culture is neither a substitute nor a screen for blood culture. Blood cultures should be performed in any potentially septic animal, especially those that are considered immunosuppressed., (Copyright © 2018 American Society for Microbiology.)

The aim of this study was to assess if the coupled analysis of the urinary protein to creatinine (UPC) ratio and of the GGT/UC ratio (the ratio between urinary γ-glutamyl transferase activity and urinary creatinine) may be used in treated leishmaniotic dogs to differentiate dogs with transient impairment of tubular function from dogs with persistent tubular damage. To this aim, 40 urine from 10 proteinuric and leishmaniotic dogs that at the first visit had high GGT/UC ratio, consistent with tubular damage, were collected and analyzed before treatments and 2, 4 and 6 weeks after treatment with N-methylglucamine antimoniate and allopurinol. Compared with pre-treatment values, at the end of the study period the UPC ratio decreased only in 5/10 dogs, which, however, were still proteinuric or borderline proteinuric. Conversely, the GGT/CU ratio decreased in 8/10 dogs and in 3 of them the values at the end of the study period were below the threshold consistent with tubular proteinuria. The GGT/UC values at 6 weeks was significantly lower than before treatment. However, transient increases were frequent for both the analytes. These results indicate that in most of the dogs that remain proteinuric after treatment, likely due to the persistent glomerular damage, the GGT/UC ratio tends to normalize. This suggests that in these dogs tubular proteinuria at admission depends on functional impairment of tubular cells likely due to the overflow of proteins from damaged glomeruli. However, tubular proteinuria occasionally persists, suggesting that tubulointerstitial damages persist even in dogs responsive to treatments., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

OBJECTIVE To examine the effect of 24 hours of refrigeration on urine samples collected from dogs with signs of urinary tract infection (UTI). DESIGN Prospective cross-sectional study. ANIMALS 104 dogs with signs consistent with UTI that had a urine sample collected via cystocentesis as part of their diagnostic workup. PROCEDURES A 1-mL aliquot of each urine sample was refrigerated at 5°C for 24 hours in a plain glass tube, then processed for quantitative bacterial culture (QBC). A 0.5-mL aliquot was added to 3 mL of tryptic soy broth (TSB) and refrigerated at 5°C for 24 hours, then processed for QBC. The remaining portion was immediately processed for QBC, with results reported as numbers of bacterial colony-forming units (CFUs). Sensitivity of the QBC for detection of bacteria (and therefore UTI) was determined for sample refrigeration in the 2 conditions, compared with immediate processing (reference standard). RESULTS Bacterial growth was identified in 35.6% (n = 37), 33.7% (35), and 31.7% (33) of the immediately processed, refrigerated, and refrigerated-in-TSB urine samples, respectively. Sample refrigeration without TSB resulted in no significant difference in CFU counts relative to immediate processing; however, the sensitivity of this method was 95% (35/37). Sample refrigeration with TSB resulted in significantly lower CFU counts, and sensitivity was only 89% (33/37). CONCLUSIONS AND CLINICAL RELEVANCE Canine urine samples collected for bacterial culture should be immediately submitted for testing. Although CFU counts for refrigerated and immediately processed samples were statistically similar in this study, sample refrigeration in enrichment broth resulted in imperfect sensitivity for UTI detection and is not recommended.

A modified TaqMan real-time polymerase chain reaction targeting a 138bp fragment within the lipl32 gene was developed to identify exclusively pathogenic Leptospira spp. in dog urine samples. Thirty-five samples from dogs with suspected clinical leptospirosis and 116 samples from apparently healthy dogs were tested for presence of leptospiral DNA using the TaqMan-based assay. The results were compared with those from a well-established conventional PCR targeting the 16S RNA encoding gene associated with nucleotide sequencing analysis. The overall agreement between the assays was 94.8% (confidence interval [CI] 95% 88-100%). The newly developed assay presented 91.6% (CI 95% 71.5-98.5%) relative sensitivity (22[+] lipl32 PCR/24[+] 16S RNA and sequencing), 100% (CI 95% 96.3-100%) relative specificity and 98.7% accuracy (CI 95% 94.8-100%). The lipl32 assay was able to detect and quantify at least 10 genome equivalents/reaction. DNA extracted from 17 pathogenic Leptospira spp., 8 intermediate/saprophytic strains and 21 different pathogenic microorganisms were also tested using the lipl32 assay, resulting in amplification exclusively for pathogenic leptospiral strains. The results also demonstrated high intra and inter-assay reproducibility (coefficient of variation 1.50 and 1.12, respectively), thereby qualifying the newly developed assay as a highly sensitive, specific and reliable diagnostic tool for leptospiral infection in dogs using urine specimens., (Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin infection and solid organ abscesses. It is caused by Burkholderia pseudomallei, which in the United States is classified as a select agent, with "potential to pose a severe threat to both human and animal health, to plant health or to animal and plant products" (Federal Select Agent Program, http://www.selectagents.gov/, accessed 22 September 2016). Burkholderia pseudomallei is found in soil and surface water in the tropics, especially South-East Asia and northern Australia, where melioidosis is endemic. Human cases are rare in the United States and are usually associated with travel to endemic areas. Burkholderia pseudomallei can also infect animals. We describe a multijurisdictional public health response to a case of subclinical urinary B. pseudomallei infection in a dog that had been adopted into upstate New York from a shelter in Thailand. Investigation disclosed three human contacts with single, low-risk exposures to the dog's urine at his residence, and 16 human contacts with possible exposure to his urine or culture isolates at a veterinary hospital. Contacts were offered various combinations of symptom/fever monitoring, baseline and repeat B. pseudomallei serologic testing, and antibiotic post-exposure prophylaxis, depending on the nature of their exposure and their personal medical histories. The dog's owner accepted recommendations from public health authorities and veterinary clinicians for humane euthanasia. A number of animal rescue organizations actively facilitate adoptions into the United States of shelter dogs from South-East Asia. This may result in importation of B. pseudomallei into almost any community, with implications for human and animal health., (© 2018 Blackwell Verlag GmbH.)

The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr). Statistically significant difference in KIM/uCr (p = 0.0007) and GGT/uCr (p < 0.0001) was found among the study groups. Area under the curve (AUC) for KIM-1/uCr and GGT/uCr as predictors of AKI was 0.81 and 0.91 respectively. Values of KIM-1/uCr of 0.73 ng/mg and of GGT/uCr of 54.33 showed the best combination of sensitivity and specificity (75% and 75.6%; 85.7% and 89.1% respectively). A significant positive correlation (p < 0.0001) between KIM-1/uCr and GGT/uCr was found. Both urine KIM-1/uCr and GGT/uCr seemed to be potentially good markers for the diagnosis of AKI. Dogs with AKI showed significantly higher levels of urine KIM-1/uCr and urine GGT/uCr, compared with healthy dogs. Caution should be used in the evaluation of elevated urine KIM-1/uCr and GGT/uCr in dogs with pre-existing CKD and/or LUTD. Urine KIM-1/uCr and GGT/uCr might have a significant clinical utility, as complementary test, particularly in diagnosis early, non-azotemic stages of AKI.

Background: The dipstick is a first-line and inexpensive test that can exclude the presence of proteinuria in dogs. However, no information is available about the analytical variability of canine urine dipstick analysis., Objectives: The aim of this study was to assess the analytical variability in 2 dipsticks and the inter-operator variability in dipstick interpretation., Methods: Canine urine supernatants (n = 174) were analyzed with 2 commercially available dipsticks. Two observers evaluated each result blinded to the other observer and to the results of the other dipstick. Intra- and inter-assay variability was assessed in 5 samples (corresponding to the 5 different semi-quantitative results) tested 10 consecutive times over 5 consecutive days. The agreement between observers and between dipsticks was evaluated with Cohen's k test., Results: Intra-assay repeatability was good (≤3/10 errors), whereas inter-assay variability was higher (from 1/5 to 4/5 discordant results). The concordance between the operators (k = 0.68 and 0.79 for the 2 dipsticks) and that of the dipsticks (k = 0.66 and 0.74 for the 2 operators) was good. However, 1 observer and 1 dipstick overestimated the results compared with the second observer or dipstick. In any case, discordant results accounted for a single unit of the semi-quantitative scale., Conclusions: As for any other method, analytic variability may affect the semi-quantitation of urinary proteins when using the dipstick method. Subjective interpretation of the pad and, to a lesser extent, intrinsic staining properties of the pads could affect the results. Further studies are warranted to evaluate the effect of this variability on clinical decisions., (© 2018 American Society for Veterinary Clinical Pathology.)

Background: Leptospirosis is an important worldwide zoonosis. This disease is caused by pathogenic species of the genus Leptospira which are maintained in the environment via chronic renal infection of carrier animals which can be asymptomatic excretors of the organisms in their urines and become a source of infection for humans and other hosts. The prevalence of animal leptospirosis in Algiers, Algeria, is unknown., Methodology/principal Findings: Real-time PCR and standard PCR and sequencing were used to detect pathogenic Leptospira organisms in the urines of stray dogs and cats in Algiers. In the presence of appropriate controls, none of the 107 cat urine samples were positive while 5/104 (4.8%) canine urine samples (asymptomatic mixed-breed dogs, three females and two males) were positive in two real-time PCR assays targeting the rrs and hsp genes. The positivity of these samples was confirmed by partial PCR-sequencing of the rpoB gene which yielded 100% sequence similarity with Leptospira interrogans reference sequence. In this study, L. interrogans prevalence was significantly higher in dogs aged < one year (16.46% - 29.41%) than in adults (0%) (P value = 0.0001) and then in the overall dog population (2.68% - 4.8%) (P = 0.0007)., Conclusions/significance: These results suggest that dogs are maintenance hosts for zoonotic leptospirosis in Algiers, Algeria. To face this situation, effective canine vaccination strategies and raising public health awareness are mandatory. Further investigations incorporating a larger sample in more localities will be undertaken to document the epidemiology of urban animal leptospirosis in Algeria at large.

OBJECTIVE To determine the prevalence of bacteriuria (ie, a positive microbial culture result for ≥ 1 urine sample) in dogs with chronic kidney disease (CKD) and characterize findings of subclinical bacteriuria (SBU), bacterial cystitis, or pyelonephritis in these patients. DESIGN Retrospective, observational study. ANIMALS 182 dogs. PROCEDURES Medical records from January 2010 through July 2015 were reviewed to identify dogs with CKD that underwent urinalysis and urine microbial culture. Signalment, clinicopathologic data, stage of CKD according to previously published guidelines, results of urinalysis and urine culture, and abdominal ultrasonographic findings were recorded. Dogs with positive urine culture results were categorized as having SBU, bacterial cystitis, or pyelonephritis on the basis of these data. Prevalence of bacteriuria was calculated. Associations between CKD stage, presence of bacteriuria, and diagnosis category were analyzed statistically. RESULTS 33 of 182 (18.1%) dogs (40/235 [17.0%] urine samples) had positive culture results. All dogs received antimicrobials on the basis of culture and susceptibility test findings. Most positive culture results (18/40 [45%] samples) were found for dogs with SBU, followed by dogs with pyelonephritis (16/40 [40%]) and cystitis (6/40 [15%]). Escherichia coli was the most frequently observed isolate (29/40 [73%] cultures from 25/33 dogs). The CKD stage was not associated with presence of bacteriuria or diagnosis category. CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of positive urine culture results in dogs with CKD was lower than that reported for dogs with some systemic diseases that may predispose to infection. Prospective research is needed to assess the clinical importance of SBU in dogs with CKD.

Objectives: To determine if a urine sodium concentration could be used to rule out hypoadrenocorticism in hyponatraemic dogs., Materials and Methods: Medical records were reviewed for hyponatraemic dogs (serum sodium<135 mmol/L) that had recorded urine sodium concentrations. Twenty hyponatraemic dogs were included: 11 diagnosed with classical hypoadrenocorticism and nine with non-adrenal causes of hyponatraemia. A Wilcoxon rank-sum test was used to compare results between groups., Results: No dog with hypoadrenocorticism had a urine sodium concentration less than 30 mmol/L. Urine sodium concentration in dogs with hypoadrenocorticism was significantly higher (median 103 mmol/L, range: 41 to 225) than in dogs with non-adrenal illness (median 10 mmol/L, range: 2 to 86) (P<0·0005). Serum sodium concentrations were not significantly different between dogs with hypoadrenocorticism and dogs with non-adrenal illness., Clinical Significance: These results suggest that urine sodium concentrations can be used to prioritise a differential diagnosis of hypoadrenocorticism in hyponatraemic dogs. A urine sodium concentration less than 30 mmol/L in a hyponatraemic dog makes classical hypoadrenocorticism an unlikely cause of the hyponatraemia. Nevertheless, because of the small sample size our results should be interpreted with caution and a larger follow-up study would be valuable., (© 2017 British Small Animal Veterinary Association.)

Background: Clinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work-up could optimize treatment and reduce the risk of inappropriate use of antibiotics., Hypothesis/objectives: To describe and evaluate the impact of diagnostic work-up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease., Animals: One hundred and fifty-one dogs presenting to 52 Danish veterinary practices., Methods: Prospective, observational study. Clinical signs, diagnostic work-up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT., Results: In the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty-one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over-prescribed and 2% under-prescribed. Inappropriate use of second-line agents was found in 57% of the UTI cases. Performing microscopy-but not culture-significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in-house microscopy and culture were 64.5 and 77%, respectively., Conclusions and Clinical Importance: Over-prescription of antibiotics was common among dogs with suspected UTI, regardless of the diagnostic work-up performed. Test inaccuracy under practice conditions and incoherence between diagnostic test results and decision-making both explained inappropriate and unnecessary use of antibiotics., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)