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Background: Renal disease in canine leishmaniosis is of great importance owing to increased risk of mortality. In human visceral leishmaniosis, monocyte chemoattractant protein-1 (MCP-1) has been used as a marker of renal damage and inflammation. The purpose of this study was first to determine the serum MCP-1 and urinary MCP-1-to-creatinine ratio (uMCP-1/Cr) in healthy dogs and dogs with leishmaniosis at diagnosis, and second to determine whether these markers can differentiate disease severity at diagnosis., Methods: In total, 19 healthy seronegative dogs and 38 dogs with leishmaniosis were included in the study. Dogs with leishmaniosis were classified as LeishVet clinical staging and as International Renal Interest Society (IRIS) staging. Serum and urinary MCP-1 concentrations were measured with an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve determined disease severity at diagnosis between two LeishVet groups (Stage II versus stage III and IV)., Results: Dogs in Leishvet stages IIb, III, and IV had a median serum MCP-1 and uMCP-1/Cr concentration higher than healthy dogs (P < 0.0001). No statistical differences were found in serum MCP-1 and uMCP-1/Cr between dogs in LeishVet stage IIa and healthy dogs. The dogs in LeishVet stage IV had significantly higher serum MCP-1 and uMCP-1/Cr compared with the dogs in LeishVet stage IIa (P < 0.0001). Serum MCP-1 and uMCP-1 were significantly higher in dogs in IRIS stage I and II + III + IV compared with healthy dogs. Dogs stage II + III + IV of IRIS had a significantly higher serum MCP-1 compared with dogs in IRIS stage I (P < 0.0001). The area under the ROC curve for serum MCP-1 was 0.78 [95% confidence interval (CI) 0.64-0.93] and for uMCP-1/Cr it was 0.86 (95% CI, 0.74-0.99). The optimal cutoff value for serum MCP-1 and uMCP-1/Cr was 336.85 pg/ml (sensitivity of 79% and specificity of 68%) and 6.89 × 10 -7 (sensitivity of 84% and specificity of 79%), respectively., Conclusions: Serum MCP-1 and uMCP-1/Cr are increased in dogs with leishmaniosis compared with healthy dogs, suggesting the presence of inflammation and renal injury. Serum MCP-1 and uMCP-1/Cr were more elevated in the advanced stages of the disease compared with the moderate stages and, therefore, can be markers of the severity of the disease process., (© 2024. The Author(s).)

Background: Despite the prevalence of echogenic foci floating in the urinary bladder seen in ultrasonography in dogs, surprisingly little has been written on its significance, including its potential association with urinalysis. The objective of the study was to determine the diagnostic value of the echogenic foci floating in urinary bladders in dogs., Results: - Cystosonography was performed on 45 dogs. Bladder contents were examined and divided into positive (containing echogenic particles) and negative (absent echogenic particles) groups according to the presence and absence of floating echogenic particles. Five mL of urine was collected via cystocentesis. Urine analysis and culture were done and the relationship between ultrasound evaluation and urinalysis results was investigated. In dogs with bladder echogenic particles in ultrasonography, the prevalence of hematuria, pyuria, bacteriuria, and lipiduria were 88.9%, 92.6%, 29.6%, and 70.3%, respectively. However, in dogs in which echogenic particles were not observed in their bladders, the prevalence of hematuria, pyuria, bacteriuria, and lipiduria was 77%, 50%, 5.5%, and 77%, respectively. There was a significant association between bladder debris and positive urine culture, with an odds ratio of 7.15 (95% confidence interval: 0.81-63.28) compared with matched controls. Furthermore, there was a significant relationship between the presence of floating echogenic particles with pyuria, and urine color ( p ≤ 0.05)., Conclusion: In conclusion, the present results showed the detection of bladder debris on ultrasound can be a predictor for pyuria and positive urine culture in dogs., (© 2024. The Author(s).)

Current diagnostic methods for canine urothelial carcinoma (UC) are technically challenging or can lack specificity, hence there is a need for novel biomarkers of UC. To this end, we analysed the microRNA (miRNA) cargo of extracellular vesicles (EVs) from urine samples of dogs with UC to identify candidate miRNA biomarkers. Urine was fractionated using ultrafiltration combined with size-exclusion chromatography and small RNA sequencing analysis was performed on both the EV enriched and (EV free) protein fractions. A greater number of candidate miRNA biomarkers were detected in the EV fraction than the protein fraction, and further validation using droplet digital PCR (ddPCR) was performed on the EV enriched fraction of a second cohort of dogs with UC which indicated that miR-182, miR-221 and miR-222 were significantly overrepresented in dogs with UC when compared with healthy dogs and dogs with urinary tract infections. Pathway analysis confirmed that these three miRNAs are involved in cancer. In addition, their potential downstream gene targets were predicted and PIK3R1, a well-known oncogene is likely to be a shared target between miRNA-182 and miRNA-221/222. In summary, this study highlights the potential of urinary EV-associated miRNAs as a source of biomarkers for the diagnosis of canine UC., (© 2024. The Author(s).)

Background: Syndecan-1 (SDC1) is an established marker of endothelial glycocalyx shedding. Most research on SDC1 has focused on plasma or serum concentrations, and little is known about urine concentrations., Objectives: Measure urinary SDC1 concentrations in dogs undergoing anesthesia with either sevoflurane or isoflurane and assess the effects of anesthesia duration and IV crystalloids on urinary SDC1 concentrations., Animals: Thirty-one client-owned dogs undergoing anesthesia for magnetic resonance imaging (MRI) with or without surgery for suspected intervertebral disk disease (IVDD) were used., Methods: Dogs with suspected IVDD were randomized to undergo anesthesia with either sevoflurane or isoflurane. Urine was collected before and immediately after anesthesia for the analysis of SDC1. Urinary creatinine concentrations also were measured, and the ratio of urinary SDC1 to urinary creatinine (USCR) was used to account for dilution., Results: Median (range) USCR was significantly higher after anesthesia compared with baseline for all groups combined (P < .05). No significant difference was found between the groups for age, sex, weight, and type of anesthesia. Multiple regression analysis of the effect of the independent variables inhalant type, age, weight, sex, anesthesia time, surgery, and quantity of IV fluids on the dependent variable SDC1 found that only the quantity of IV fluids significantly predicted a change (P < .001)., Conclusions and Clinical Importance: The total volume of lactated Ringer's solution administered to anesthetized dogs may affect USCR. Further investigations are warranted to evaluate the relationship between IV fluids and SDC1., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Introduction and Objective: Escherichia coli is one of the most common bacteria isolated from urine samples collected from dogs and cats with urinary tract infection (UTI). Uncomplicated UTIs in dogs and cats can be treated with short courses of first-line antimicrobial drugs, e.g. amoxicillin, amoxicillin with clavulanic acid, or trimethoprim/sulfonamide. Recurrent or complicated UTIs often require long-term treatment with broad-spectrum antibiotics. However, the choice of drug should be based on antimicrobial susceptibility., Material and Methods: Between March - September 2022, E. coli isolates cultured from the urine of 66 dogs and 41 cats with UTI symptoms were tested for antimicrobial resistance by using Minimum Inhibitory Concentration (MIC). Antimicrobial susceptibility was tested for ampicillin, ampicillin/sulbactam, cefazolin, cefuroxime, aztreonam, gentamycin, amikacin, colistin, trimethoprim/sulfamethoxazole, ciprofloxacin, chloramphenicol and tetracycline., Results: The highest prevalence of resistance was documented for ampicillin (68% in dogs, 100% in cats) and ampicillin with sulbactam (59% in dogs, 54% in cats). The most common antimicrobial resistance patterns of E. coli were ampicillin alone (12 isolates, 29.3% in cats) and beta-lactams, including aztreonam (14 isolates, 21.2% in dogs)., Conclusions: High resistance to aztreonam (61% and 32% of isolates from dogs and cats, respectively), other beta-lactams, and fluoroquinolones should cause be alarm due to zoonotic potential and cross-transmission of antimicrobial-resistant microorganisms between animals and humans.

Objective: To determine the accuracy of 4 preoperative parameters (signalment, urinalysis, urine microbiological culture, and digital radiography) in predicting urocystolith composition, compare accuracy between evaluators of varying clinical experience and a mobile application, and propose a novel algorithm to improve accuracy., Animals: 175 client-owned dogs with quantitative analyses of urocystoliths between January 1, 2012, and July 31, 2020., Methods: Prospective experimental study. Canine urocystolith cases were randomly presented to 6 blinded "stone evaluators" (rotating interns, radiologists, internists) in 3 rounds, each separated by 2 weeks: case data alone, case data with a urolith teaching lecture, and case data with a novel algorithm. Case data were also entered into the Minnesota Urolith Center mobile application. Prediction accuracy was determined by comparison to quantitative laboratory stone analysis results., Results: Prediction accuracy of evaluators varied with experience when shown case data alone (accuracy, 57% to 82%) but improved with a teaching lecture (accuracy, 76% to 89%) and further improved with a novel algorithm (accuracy, 93% to 96%). Mixed stone compositions were the most incorrectly predicted type. Mobile application accuracy was 74%., Clinical Relevance: Use of the 4 preoperative parameters resulted in variable accuracy of urocystolith composition predictions among evaluators. The proposed novel algorithm improves accuracy for all clinicians, surpassing accuracy of the mobile application, and may help guide patient management.

Background: The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients., Objectives: Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria., Animals: Urine samples from 308 dogs and 70 cats., Methods: Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021., Results: Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively., Conclusions and Clinical Importance: Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To collect voided urine from dogs with clinical signs of lower UTI and determine the diagnostic performance of a commercially available rapid immunoassay (RIA) immediately after urine collection and after refrigeration at 4 and 24 hours., Animals: 40 client-owned dogs., Methods: Aerobic urine culture was performed on urine collected by cystocentesis. Urine samples were collected by voiding, and the RIA performed in triplicate within 30 minutes (time 0) and again in triplicate after 4 and 24 hours of refrigeration. Test precision and agreement between culture results and RIA results at each time point were determined, and factors possibly associated with false results investigated., Results: 14 of 40 dogs (35%) had UTI verified by aerobic urine culture, and all had positive RIA. Three dogs had false positive RIA results. Sensitivity, specificity, positive predictive value, and negative predictive value of the RIA were 100, 88%, 82%, and 100%, respectively, and results were not different after 4 and 24 hours of refrigeration. Precision was excellent., Clinical Relevance: This point-of-care RIA, performed on voided urine refrigerated up to 24 hours, rapidly and accurately identifies bacteriuria in dogs with lower urinary tract clinical signs, inexpensively.

Standard visual urine dipstick analysis (UDA) is performed routinely in veterinary medicine; results can be influenced by both the operator and the method. We evaluated the agreement of results for canine and feline urine samples analyzed using a 10-patch dipstick (Multistix10SG; Siemens), both visually under double-anonymized conditions by students and a laboratory technician, and with an automated device (AD; Clinitek Status, Siemens). The mean concordance for semiquantitative urinalysis results between students and the technician and between students and the AD was fair (κ0.21-0.40) in dogs and cats; concordance was moderate between the technician and the AD (κ0.41-0.60) in dogs and good (κ0.61-0.80) in cats. For pH, the mean concordance between students and the technician and between the technician and the AD was good (ρ0.80-0.92) in dogs and cats; concordance was good between students and the AD (ρ0.80-0.92) in dogs and moderate (ρ0.59-0.79) in cats. Repeatability was higher ( p  < 0.001) for the technician and the AD than for a student. We found good agreement between UDA performed by an experienced operator and an AD in dogs and cats but found low reproducibility and low repeatability for urinalysis performed by an inexperienced operator.

Background: No recent studies have evaluated the association between clinical signs of lower urinary tract disease (LUTD) and positive urine culture in dogs with diabetes mellitus., Objective: Determine the prevalence of subclinical bacteriuria (ie, positive urine culture without signs of LUTD) in dogs with diabetes mellitus., Animals: One hundred seven dogs with diabetes mellitus were evaluated at a university veterinary hospital., Methods: Retrospective study evaluating diabetic dogs with a single sample paired urinalysis and urine culture. Relationship between the presence of signs of LUTD, pyuria, and bacteriuria and urine culture results were compared using Fisher exact testing., Results: Fifteen dogs (14%) had a positive urine culture via cystocentesis or free catch, of which 8 (53%) had pyuria, and 4 (27%) had signs of LUTD. Of the 88 dogs (82%) without signs of LUTD, 11 (13%) had a positive culture. A significant association was found between a positive urine culture and pyuria (OR infinity; 95% CI 20.34-infinity, P < .00001) and bacteriuria (OR infinity; 95% CI 164.4-infinity, P < .00001). No association was found between urine culture results and signs of LUTD (OR 1.87; 95% CI 0.59-6.85, P = .46)., Conclusion and Clinical Importance: Subclinical bacteriuria occurred in this cohort of dogs, and our findings reinforce the recommendation that urine cultures should not be routinely performed in diabetic dogs particularly if pyuria and bacteriuria are absent., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To evaluate the urine cortisol-to-creatinine ratio (UCCR) for the diagnosis of hypoadrenocorticism (HA) in dogs and to determine whether the method of urine cortisol measurement affects results., Animals: 41 dogs with naturally occurring HA and 107 dogs with nonadrenal illness., Procedures: Urine samples were prospectively collected from dogs undergoing testing for HA. Urine cortisol concentrations were measured at a veterinary diagnostic laboratory using either a radioimmunoassay (RIA) or a chemiluminescent immunoassay (CLIA). Receiver operating characteristic (ROC) curves were constructed to assess UCCR performance by both methods for HA diagnosis. Sensitivities, specificities, accuracies, and predictive values were calculated for various cutpoints., Results: The areas under the ROC curves for UCCR diagnosis of HA were 0.99 (95% CI, 0.98 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) when urine cortisol was determined by RIA and CLIA, respectively. An RIA UCCR of ≤ 2 was 97.2% sensitive, 93.6% specific, and 94.7% accurate for HA diagnosis, whereas a CLIA UCCR of ≤ 10 was 100% sensitive, specific, and accurate. An RIA UCCR > 4 and a CLIA UCCR of > 10 had negative predictive values of 100%., Clinical Relevance: The UCCR was an accurate diagnostic test for HA in this study population, although equivocal results are possible. Case characteristics, method of cortisol measurement, and laboratory-specific cutpoints must be considered when interpreting results.

The objective of this study was to evaluate the benefits and inherent risks of dental cleaning procedures, based on serum and urine biomarkers for kidney function and tissue damage, in dogs and cats. Thirty-one asymptomatic, mostly older dogs (14 neutered male and 17 ovariohysterectomized female dogs of various breeds between 3 and 14 years old) and cats (19 neutered male and 12 ovariohysterectomized female domestic short hair cats between 2 and 16 years old) diagnosed with periodontal disease on physical exam, and recommended by their veterinarian to have dental cleaning under general anesthesia were evaluated in a prospective study. Serum and urine samples were collected from dogs and cats 1 week before, 6 hours after, and again 1 week after the dental cleaning procedure. Samples were analyzed for biomarkers of kidney function [serum creatinine (Cr), symmetric dimethylarginine (SDMA), and blood urea nitrogen (BUN), and urine for specific gravity (USG) and protein:creatinine (UPC) ratio]. A panel of biomarkers for renal tissue damage was also assessed [serum β-aminoisobutyric acid (BAIB), and urine cystatin B and clusterin]. Samples collected one week before dental cleaning procedures showed that increased age and severity of dental disease were linked to abnormal kidney function biomarker values (age: elevated SDMA and Cr concentrations and isosthenuric USG values; disease severity: elevated UPC ratios) as well as elevated urine cystatin B and clusterin concentrations. Directly after the dental cleaning procedure, an increased number of cats with elevated SDMA concentrations was observed (specifically in cats with longer duration of dental procedures). Extended duration of dental procedures (≥60 min) was linked to increased urine cystatin B and clusterin concentrations, whereas shorter duration procedures was linked to decreased urine cystatin B and clusterin. Higher SDMA concentrations persisted in cats one week after the dental cleaning procedures and were linked to elevated UPC ratios one week before cleaning procedures. In conclusion, the results of this study indicate a link between severity of dental disease, renal tissue injury, and impaired renal function. Longer duration dental procedures in cats may carry inherent risks of kidney injury and impaired renal function., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: two of the authors have an affiliation (GF, MY) to the commercial funders of this research, as employees of IDEXX Laboratories, Inc. (https://www.idexx.com/en/). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Bacterial urinary tract infection (UTI) is a common condition affecting dogs. Urine culture and antimicrobial susceptibility test, associated with the identification of underlying cause, are of primary importance in order to select a correct treatment, especially in presence of comorbidities. Two cases of immunecompromised dogs affected by urinary tract infection (UTI) have been described: the first, probably immunosuppressed due to old age, was in poor body condition, with severe odontolithiasis and periodontitis; the second was affected by chronic kidney disease in advanced stage. Urine cultures isolated two rare and atypical pathogens, Moellerella wisconsensis and Brevundimonas vesicularis, both showing sensitivity versus floroquinolones which were selected for the treatment. After a 4 weeks treatment, a second culture demonstrated the resolution of infection in both cases, in absence of clinical signs.To date neither of the two bacteria have been reported as cause of UTI in dog.

Background: Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs., Results: Thirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 μmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P <  0.0001, P <  0.0001, P = 0.01), 24 h (P <  0.001, P <  0.001, P = 0.002) and 36 h (P <  0.001, P <  0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls., Conclusion: Urinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.

Background: Quantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR)., Objectives: This study aimed to compare the UPCR obtained by three types of analyzers (automated wet chemistry analyzer, in-house dry chemistry analyzer, and dipstick reading device) and investigate whether the differences could affect clinical decision process., Methods: Urine samples were collected from 115 dogs. UPCR values were obtained using three analyzers. Bland-Altman and Passing Bablok tests were used to analyze agreement between the UPCR values. Urine samples were classified as normal or proteinuria based on the UPCR values obtained by each analyzer and concordance in the classification evaluated with Cohen's kappa coefficient., Results: Passing and Bablok regression showed that there were proportional as well as constant difference between UPCR values obtained by a dipstick reading device and those obtained by the other analyzers. The concordance in the classification of proteinuria was very high (κ = 0.82) between the automated wet chemistry analyzer and in-house dry chemistry analyzer, while the dipstick reading device showed moderate concordance with the automated wet chemistry analyzer (κ = 0.52) and in-house dry chemistry analyzer (κ = 0.53)., Conclusions: Although the urine dipstick test is simple and a widely used point-of-care test, our results indicate that UPCR values obtained by the dipstick test are not appropriate for clinical use. Inter-instrumental variability may affect clinical decision process based on UPCR values and should be emphasized in veterinary practice., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Veterinary Science.)

Thoraco-lumbar intervertebral disc extrusion is a common condition seen in veterinary practice. Although there are different surgical techniques described for decompression, most of these techniques are based on the surgeon's preference or experience rather than clinical research. Our objective was to determine the clinical outcomes, using return to ambulation and micturition, as well as complication rates, in a large cohort of dogs by using a mini-hemilaminectomy for decompression of the thoraco-lumbar spinal cord with Hansen type I thoraco-lumbar intervertebral disc extrusions (IVDE). A retrospective study was performed on dogs presented for acute thoraco-lumbar IVDE undergoing surgical decompression. In total, 252 spinal decompression surgeries were performed. The recovery rates for patients graded with a modified Frankel score (MFS) of 5 to 0 were 100%, 99%, 100%, 96%, 86% and 64%, respectively. The mean days to micturition across all the MFS 5-0 were 1.5 (standard deviation [SD] ± 0.7), 1.8 (SD ± 1), 4.3 (SD ± 1.7), 6.4 (SD ± 2.2), 9.3 (SD 3) and 11.9 (SD ± 2.2), respectively. The mean days to ambulation across all the groups 5-0 were 2 (SD ± 0.7), 2.6 (SD ± 1), 7.6 (SD ± 4.4), 10.1 (SD ± 2.5), 16.1 (SD ± 2.9) and 19.3 (SD ± 2.6), respectively. Postoperative complications were seen in 32 of the surgeries, with a complication rate of 13%. Minor complications accounted for 38% of all complications, and major complications constituted 62% of all complications. In total, 15 dogs died or were euthanised as a direct result of thoraco-lumbar disc extrusion or the surgical procedure, with a mortality rate of 6% across all groups. A mini-hemilaminectomy provides similar clinical outcomes described in the literature for other methods of spinal cord decompressive surgery, and it also provides patients with similar short-term outcomes to other described decompressive surgical techniques in the dog, which have been described in the literature.

Background: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. The kidney is known to be the main source of soluble alpha-klotho and the principal regulator of its concentration. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD., Results: Serum and urinary alpha klotho concentrations were measured by a commercially available canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal-Wallis test. Spearman's correlation coefficient was used to evaluate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations. The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD was significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and serum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure., Conclusions: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho is associated with CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Although serum klotho concentration was negatively correlated with sSDMA levels, it was not apparently related to IRIS CKD stage or other parameters known to be associated with CKD.

Suspected bacterial urinary tract infections (UTI) are a common cause of overuse and misuse of antimicrobials. A bedside diagnostic test that could accurately predict urine culture results would prevent antimicrobial overuse, but accurate biomarkers have not yet been identified in veterinary medicine. The objective of this study was to evaluate urine myeloperoxidase (uMPO) as a rapidly available, accurate marker to predict urine culture results. We hypothesized that uMPO would be higher in dogs with a positive urine culture than in dogs with a negative urine culture, and that uMPO could be used to aid in the accurate diagnosis of significant bacteriuria. Urine samples were collected from a veterinary university clinical pathology lab. uMPO concentration was measured using a commercially available canine myeloperoxidase (MPO) enzyme-linked immunosorbent assay (ELISA). Following validation, samples from 98 dogs that had a urinalysis and urine culture performed as part of their diagnostic investigation were included. Forty-seven dogs had a negative urine culture and fifty-one dogs had a positive urine culture. uMPO levels were significantly higher in samples that had a positive culture (median 2.13 ng/ml; IQR 0.98-7.07) versus samples that had a negative culture (median 1.07 ng/ml; IQR 0.52-1.84)(p < 0.005). Based on receiver-operator characteristic, a cutoff of 0.55 ng/ml was chosen to maximize sensitivity and specificity. Using a cutoff of 0.55 ng/ml, uMPO had a sensitivity of 70% and specificity of 69% to determine the presence of a positive culture. However, the degree of overlap between groups may preclude the use of this test as a surrogate for urine culture in a clinical setting., Competing Interests: The authors have declared that no competing interests exist.

Nonadrenal diseases (NAD), including congestive heart failure (CHF), can affect the conversion of cortisone to cortisol favoring the production of cortisol's urinary downstream metabolites 5α/5β-tetrahydrocortisol (THF) relative to tetrahydrocortisone (THE). We hypothesized that healthy dogs would have lower urinary levels of cortisol, cortisone, THF, and THE than dogs with hypercortisolism (HC) or CHF, and the latter would have higher urinary levels of THF and lower THE than dogs with HC. Four, 9, and 8 dogs with HC, CHF, and normal health, respectively, were included in a pilot prospective cross-sectional study. A single morning voided urine sample was analyzed for urinary cortisol metabolites by liquid chromatography-mass spectrometry. The percentages of conjugated urinary metabolites were significantly higher in dogs with CHF than in healthy dogs ( p  = 0.001), and not different in HC dogs ( p  = 0.07). Log-transformed urine cortisol metabolites-to-creatinine ratios in healthy dogs were significantly lower than the 2 other groups ( p  < 0.001). The urinary free THE:THF ratio was significantly higher ( p  < 0.001) than the urinary total and conjugated THE:THF ratios. Health status did not affect the total, conjugated, and free THE:THF ratios ( p  = 0.61). Additional studies are needed to investigate differences in cortisol metabolites between dogs with HC and NAD to accurately discriminate between the groups.

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid ( p < 0.001), serotonin, indoxyl sulfate ( p < 0.01), and kynurenic acid ( p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine ( p < 0.001), and epinephrine ( p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Korean Society of Veterinary Science.)

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.)

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.

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.

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.

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.)

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.)

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.)

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.

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.)

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.

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.)

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.)

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.)

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.

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.)

Background: Monitoring urine protein:creatinine ratios (UPC) in dogs with protein-losing nephropathy (PLN) is challenging because of day-to-day variation in UPC results., Hypothesis/objectives: Determine whether single, averaged, or pooled samples from PLN dogs receiving medical treatment yield comparable UPCs, regardless of degree of proteinuria., Animals: Twenty-five client-owned PLN dogs receiving medical treatment., Methods: UPC ratios were prospectively measured in each dog utilizing 3 methods: single in-hospital sample (day 3), average sample (days 1-3), and pooled sample (equal pooling of urine from days 1-3). Bland-Altman analysis was performed to evaluate agreement between methods for all dogs, as well as in subgroups of dogs (UPC ≤4 or UPC >4)., Results: For all dogs, Bland-Altman log-transformed 95% limits of agreement were -0.07-0.18 (single versus pooled UPC), -0.06-0.16 (single versus average UPC), and -0.06-0.04 (pooled versus average UPC). For dogs with UPC ≤4, Bland-Altman 95% limits of agreement were -0.42-0.82 (single versus pooled UPC), -0.38-0.76 (single versus average UPC), and -0.27-0.25 (pooled versus average UPC). For dogs with UPC >4, Bland-Altman 95% limits of agreement were -0.17-2.4 (single versus pooled UPC), -0.40-2.2 (single versus average UPC), and -0.85-0.43 (pooled versus average UPC)., Conclusions and Clinical Importance: UPC ratios from all methods were comparable in PLN dogs receiving medical treatment. In PLN dogs with UPC >4, more variability between methods exists likely because of higher in-hospital results, but whether this finding is clinically relevant is unknown., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR., Results: Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients., Conclusions: Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted.

OBJECTIVE To evaluate the clinical performance of a commercially available compartmentalized urine culture and antimicrobial susceptibility test plate (CCSP) for identification of canine bacteriuria and assessment of isolate antimicrobial susceptibility. DESIGN Cross-sectional study. ANIMALS 71 dogs. PROCEDURES Urine samples (n = 84) were divided into 3 aliquots. One aliquot (reference culture) was plated on culture medium ≤ 1 hour after collection for quantitative culture and testing by standard laboratory methods, another was stored at 4°C for 24 hours (to mimic storage practices at primary care facilities) and then processed by standard methods, and the third was applied to a CCSP ≤ 1 hour after collection to be processed and interpreted according to manufacturer instructions. Results were compared with those for reference culture, which was used as the criterion reference standard. Sensitivity, specificity, positive and negative predictive values, and agreement between methods was evaluated. RESULTS 43 isolates (25 single and 9 multiple isolates) were identified in 34 reference cultures. All results for stored cultures were identical to those for reference cultures. Overall sensitivity of the CCSP method to detect bacteriuria was 93%, and specificity was 100%. Thirty-three of 43 (77%) and 19 of 33 (58%) CCSP bacterial isolates were correctly identified to the genus and species level, respectively. The CCSP antimicrobial susceptibility results matched those for reference cultures for 13 of 33 (39%) isolates evaluated. CONCLUSIONS AND CLINICAL RELEVANCE Limitations of the CCSP method included inaccuracy of some antimicrobial susceptibility test results and failure to correctly identify bacteriuria in some dogs.

Background: Glucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy. Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration., Results: Untreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy., Conclusion: Influences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.