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Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment., Competing Interests: Declaration of Competing Interest Michael Coyne and Rachel Murphy are employees of IDEXX Laboratories, Inc. None of the authors had any other financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Background: Serum creatinine concentrations are higher in Greyhounds when compared with nonsighthound breeds. Greyhounds might also have higher urine creatinine concentrations compared with other breeds, which could affect urine protein-to-creatinine ratio (UPC) references., Objectives: We aimed to determine the UPC reference intervals (RIs) in healthy nonracing Greyhounds and compare this with UPC values in a group of healthy nonsighthounds and with the current International Renal Interest Society (IRIS) guidelines., Methods: The study used an observational cross-sectional design, involving clinically healthy, nonracing Greyhounds (n = 98) and nonsighthound dogs of similar weight, age, and sex (n = 24). Packed cell volumes, total solids, urine protein concentrations, serum and urine creatinine concentrations, urine specific gravity (USG) measurements, and UPCs were determined. Linear regression was used to compare urine creatinine and urine protein concentrations, relative to the USG measurements, between Greyhound and nonsighthound groups. Greyhound UPC RIs were determined using nonparametric methods and compared with UPC values in nonsighthounds and current IRIS guidelines., Results: Mean urine creatinine concentrations, adjusted for USGs, were approximately 22% higher in Greyhounds compared with nonsighthounds (P = .002). Mean urine protein concentration (P = .46) and UPC (P = .1) were not significantly different between Greyhounds and nonsighthounds. The upper limit of the Greyhound UPC RI was 0.20 or 0.42, depending on whether strict or moderate exclusion criteria were applied, respectively., Conclusions: Greyhounds have higher urine creatinine concentrations than nonsighthounds. Although the suggested RI for UPCs in Greyhounds is slightly lower than the cut-offs recommended in generic canine IRIS guidelines, this difference is not likely to be clinically significant., (© 2020 American Society for Veterinary Clinical Pathology.)

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.)

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.)

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: 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: 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.)

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.)

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.)

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: 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.)

OBJECTIVE To investigate effects of storage conditions on the canine urine protein-to-creatinine ratio (UPC) and on SDS-agarose gel electrophoresis (AGE) of urinary proteins. SAMPLE Urine specimens from 20 proteinuric (UPC > 0.5) and 20 nonproteinuric (UPC ≤ 0.2) dogs. PROCEDURES UPC and SDS-AGE were performed on urine specimens stored at room temperature (20°C) and 4°C for up to 5 days and at -20° and -80°C for up to 360 days; some specimens were subjected to 3 freeze-thaw cycles. Results were compared with those obtained for fresh urine specimens. RESULTS UPC was not affected by storage at room temperature or by freezing. A decrease in UPC was observed for specimens from nonproteinuric dogs after 5 days at 4°C (10%) and from both groups after 90 days at -20° and -80°C (≤ 20% and ≤ 15%, respectively). The SDS-AGE profiles revealed no visual changes regardless of duration of storage for specimens stored at room temperature, 4°C, and -80°C, except for 1 profile after 360 days at -80°C. Repeated freeze-thaw cycles did not affect SDS-AGE profiles. Appearance or strengthening of high-molecular-weight bands that could alter interpretation was evident in SDS-AGE profiles after storage at -20°C for ≥ 15 days (31/40 dogs). CONCLUSIONS AND CLINICAL RELEVANCE Storage of urine at -20° or -80°C for up to 1 year influenced the UPC without affecting clinical interpretation. Storage of urine specimens at -20°C impaired visual analysis of SDS-AGE. When SDS-AGE cannot be performed on fresh or recently refrigerated urine specimens, storage at -80°C is recommended.

Background: Up to 25% of elderly humans have proteinuria, often associated with underlying lesions. Data concerning the presence of proteinuria in elderly dogs is scarce., Objectives: To describe the presence and persistence of proteinuria and to compare urinary protein : creatinine ratio (UPC) between free catch and cystocentesis urine samples in apparently healthy elderly dogs., Animals: Hundred apparently healthy elderly dogs., Methods: Prospective study. Owners of 100 elderly dogs were asked to collect 2 free catch urine samples. Dogs were considered healthy based on owner's perception and an age chart, based on ideal bodyweight, was used to define dogs as senior or geriatric. UPC of urine collected by free catch and cystocentesis were compared. Overt proteinuria and borderline proteinuria were defined as UPC >0.5 and between 0.2 and 0.5, respectively, if examination of sediment did not explain proteinuria. Proteinuria was considered persistent if present at both sampling times., Results: At baseline, 71 owners succeeded in collecting urine. Eleven percent of dogs had overt proteinuria, 14% were borderline proteinuric, and 75% nonproteinuric. Thirty-seven repeated urine samples, with a median time interval of 31 days (range 10-90), were available. Nineteen percent of dogs had a persistently increased UPC (>0.2), with persistent overt proteinuria present in 8%. A strong correlation (ρ = 0.88) was found between UPC of urine collected by free catch and cystocentesis., Conclusions and Clinical Importance: As 19% of study dogs had persistent proteinuria, our findings emphasize that measurement of proteinuria should be part of geriatric health screening. For UPC in dogs, free catch urine provides a good alternative to cystocentesis., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Proteinuria is a negative prognostic indicator for dogs and cats with chronic kidney disease. A normal dog or cat should excrete very little protein and have a urine protein:creatinine ratio that is less than 0.4 or less than 0.2, respectively; persistent proteinuria above this magnitude warrants attention. Administration of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, blood pressure control and nutritional modification are considered a standard of care for renal proteinuria. Renal biopsy and administration of immunosuppressive agents should be considered in animals with glomerular proteinuria that have not responded to standard therapy. Targeted patient monitoring is essential when instituting management of proteinuria., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Urine protein loss is common in dogs with chronic kidney disease (CKD)., Hypothesis/objectives: To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD., Animals: One hunderd and eighty dogs with naturally occurring kidney disease., Methods: Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined., Results: Fractional excretions of immunogloblin M (IgM&#95;FE) and immunoglobulin G (IgG&#95;FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM&#95;FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM&#95;FE: P = .008; TEM: P = .017)., Conclusions and Clinical Importance: Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The renal biopsy tissue from a 9-month-old, male Pyrenean Mountain dog with renal disorder and severe proteinuria was examined. Ultrastructural examination revealed multilaminar splitting and fragmentation of the glomerular basement membrane (GBM) and diffuse podocyte foot process effacement. Immunofluorescent staining for α(IV) chains revealed presence of α5(IV) and complete absence of α3(IV) and α4(IV) chains in the GBM. Immunohistochemistry also revealed decreased and altered expression of nephrin and podocin in the glomeruli compared with normal canine glomeruli. These results suggested that the glomerular disease of the present case might be consistent with canine hereditary nephropathy resembling human Alport syndrome caused by genetic defect of type IV collagen, and indicated possible contribution of podocyte injury to severe proteinuria in this case.

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-β-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.

Quantification of proteinuria is a fundamental step in staging dogs with chronic kidney disease and in monitoring the course of disease or the efficacy of anti-proteinuric treatments. Analytical precision and accuracy of the proteinuria assessment could be affected by several factors such as biological variability, different operators and quality control materials. The aim of this study was to assess whether inter-laboratory variability could affect the urinary protein to creatinine (UPC) ratio and whether this variability may affect patient classification according to the International Renal Interest Society (IRIS) sub-staging system. The same urine samples were analysed in three different laboratories using different instruments and different reagent brands. The results of the three laboratories were highly correlated to each other although urinary protein (UP), urinary creatinine (UC) and the UPC ratio of one laboratory were found to be significantly higher than those of the other two. No significant differences between the other two laboratories were recorded. The concordance in classifying dogs according to the IRIS guidelines was good if all three proteinuria categories were analysed separately or if borderline proteinuric (BP) dogs were included in the proteinuric group, and very good if BP dogs were merged into the non-proteinuric group. The inter-laboratory variability in UPC ratio measurement was not so great as to impede the identification of proteinuric dogs, but may influence the estimation of the magnitude of proteinuria., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The urine protein/creatinine ratio (UPC) is a widely used screening test of glomerular barrier function. It usually requires sending urine samples to a distant laboratory, which is costly and time consuming. A point-of-care urine dipstick that could accurately measure UPC would increase test utility and utilization. The objective of this study was to determine if there was good correlation and agreement between UPC as measured by a dipstick and a laboratory analyzer. Thirty-one canines undergoing UPC measurement as part of a diagnostic workup were included in the study. A total of 2 mL of urine was collected via cystocentesis. Urine was applied to the dipstick then presented to two blinded reviewers to analyze. The remaining urine was submitted to a clinical pathology laboratory for analysis. UPC data from the dipsticks and the analyzer was converted into an ordinal scale. Correlation and agreement between the individual reviews and the analyzer was calculated. Agreement between reviewers was substantial; however, correlation and agreement between the individual reviews and the analyzer was low. On the basis of this information, use of this veterinary urinary dipstick to determine UPC cannot be recommended at this time.

Canine cardiopulmonary dirofilariosis caused by Dirofilaria immitis habitually develops as a chronic disease affecting pulmonary arteries, lung parenchyma and heart. Other organs like kidneys can also be involved. Renal pathology is a consequence of glomerulonephritis whose main sign is proteinuria. The aim of the present work is to identify proteins excreted in the urine of D. immitis infected dogs showing proteinuria, and the possible contribution of their loss to heartworm disease. Proteinuria is higher in microfilaremic (mf+) than in amicrofilaremic (mf-) dogs. Using bidimensional electrophoresis and mass spectrometry 9 different proteins from Canis lupus familiaris in the urine of both mf- and mf+ dogs were identified (serotransferrin isoform 6, serum albumin precursor, albumin, immunoglobulin gamma heavy chain D, apolipoprotein A-I, immunoglobulin lambda-like polypeptide 5-like, arginine esterase precursor, inmunoglobulin gamma heavy chain B and hemoglobin subunit alpha). Furthermore, 3 additional proteins were identified only in the urine of mf+ dogs, corresponding to dog fibrinogen alpha chain and immunoglobulin gamma heavy chain A and actin 2 homologous to a protein of Brugia malayi. The loss of these proteins and other in the urine of D. immitis infected dogs could affect the general condition of parasitized dogs through the interference in the cholesterol metabolism and O₂ transport, among other mechanisms., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Markedly overweight people can develop progressive proteinuria and kidney failure secondary to obesity-related glomerulopathy (ORG). Glomerular lesions in dogs with experimentally induced obesity are similar to those in people with ORG., Objectives: The aim of this study was to evaluate if urine protein and albumin excretion is greater in overweight and obese dogs than in dogs of ideal body condition., Methods: Client-owned dogs were screened for underlying health conditions. These dogs were assigned a body condition score (BCS) using a 9-point scoring system. Dogs with a BCS of ≥ 6 were classified as being overweight/obese, and dogs with a BCS of 4 or 5 were classified as being of ideal body weight. The urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) were then determined, and compared between 20 overweight/obese dogs and 22 ideal body weight control dogs., Results: Median UPC (0.04 [range, 0.01-0.14; interquartile range, 0.07]) and UAC (0.41 [0-10.39; 3.21]) of overweight/obese dogs were not significantly different from median UPC (0.04 [0.01-0.32; 0.07]) and UAC (0.18 [0-7.04; 1.75]) in ideal body weight dogs., Conclusions: Clinicopathologic abnormalities consistent with ORG were absent from overweight/obese dogs in this study., (© 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.)

Background: Urine is an attractive biofluid for biomarker discovery as it is easy and minimally invasive to obtain. While numerous studies have focused on the characterization of human urine, much less research has focused on canine urine., Objectives: The objectives of this study were to characterize the universal canine urinary proteome (both soluble and exosomal), to determine the overlap between the canine proteome and a representative human urinary proteome study, to generate a resource for future canine studies, and to determine the suitability of the dog as a large animal model for human diseases., Methods: The soluble and exosomal fractions of normal canine urine were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS). Biological Networks Gene Ontology (BiNGO) software was utilized to assign the canine urinary proteome to respective Gene Ontology categories, such as Cellular Component, Molecular Function, and Biological Process., Results: Over 500 proteins were confidently identified in normal canine urine. Gene Ontology analysis revealed that exosomal proteins were largely derived from an intracellular location, while soluble proteins included both extracellular and membrane proteins. Exosome proteins were assigned to metabolic processes and localization, while soluble proteins were primarily annotated to specific localization processes. Several proteins identified in normal canine urine have previously been identified in human urine where these proteins are related to various extrarenal and renal diseases., Conclusions: The results of this study illustrate the potential of the dog as an animal model for human disease states and provide the framework for future studies of canine renal diseases., (© 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.)

Renal dysfunction in dogs envenomed by poisonous snakes is currently detected using traditional serum and urinary biomarkers such as creatinine and proteinuria. However, these markers lack sensitivity at the early stages of renal dysfunction and their diagnostic accuracy is affected by pre-analytical factors commonly occurring in these dogs, such as haemolysis and haemoglobinuria. Early detection of renal dysfunction would allow for the identification of dogs requiring intensive treatment and monitoring and may help inform prognosis. The aim of this study was to evaluate the performance of several novel urinary biomarkers of glomerular dysfunction, namely, urinary albumin (uAlb), immunoglobulin G (uIgG) and C-reactive protein (uCRP) and of proximal tubular dysfunction (urinary retinol binding protein (uRBP)) compared to traditional end points in dogs with renal damage caused by snake envenomation. Biomarker results were compared between 19 dogs bitten by snakes producing either neurotoxins or cytotoxins and 10 clinically healthy controls. uAlb, uIgG, and uRBP were significantly increased in snake-envenomed dogs at presentation compared to controls, whereas only uIgG and uCRP were significantly elevated 24h post-envenomation. The urinary protein:creatinine ratio was also increased in envenomed dogs compared to controls, but because of the presence of haematuria and haemoglobinuria, differentiation between pre-renal and renal proteinuria was not possible. The results showed that these novel urinary biomarkers may assist in better detecting renal dysfunction in dogs envenomed by poisonous snakes at the acute disease stage compared to traditional laboratory endpoints., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A retrospective study was performed using 53 client owned dogs with leishmaniasis to determine whether the degree of proteinuria, evaluated by the urine protein/creatinine ratio (UP/C), changes following treatment with meglumine antimoniate and allopurinol. Medical records of dogs with leishmaniasis in clinical stage C (according to the Canine Leishmaniasis Working Group staging system) and either proteinuric or borderline proteinuric (according to the International Renal Interest Society [IRIS] staging system) were reviewed. All dogs were treated with meglumine antimoniate and allopurinol for 4-8 wk. After treatment, UP/C, total protein, and total globulin significantly decreased and albumin and the albumin/globulin ratio (A/G) increased. After treatment, 7 of the 53 dogs (13.4%) became nonproteinuric following either a proteinuric or borderline proteinuric stage. Moreover, 12 of the 53 proteinuric dogs (22.6%) changed their stage to borderline proteinuric. The antileishmaniasis treatment with meglumine antimoniate in combination with allopurinol in dogs significantly reduced the degree of proteinuria in a short period of time. The results of the current study may be useful to the veterinary practitioner in the clinical management of canine leishmaniasis (CanL) in dogs with proteinuric chronic kidney disease.

Two dipsticks developed for human use were evaluated for routine urinalysis and for detection of proteinuria in dogs (n=101), cats (n=50) and cattle (n=100). The aims were to determine their diagnostic usefulness in dogs, cats and cattle and to compare automated versus visual methods of reading. Results obtained with automated reading correlated better with reference methods than visual reading. Correlation with the reference methods was good to excellent for automated estimation of creatinine (dog: r(s)=0.86, cat: r(s)=0.83, cattle: r(s)=0.87) and pH (dog: r(s)=0.96, cat: r(s)=0.91, cattle: rs=0.94). The correlation was good for protein (dog: r(s)=0.88, cat: r(s)=0.91), glucose (cat: r(s)=0.83) and urine protein:creatinine (UPC) ratio (dog: r(s)=0.75, cat: r(s)=0.89). Estimation of proteinuria in cattle and pyuria in cats lacked specificity and detection of isosthenuria lacked sensitivity in all species. Semiquantitative estimation of UPC ratio was specific (100% and 91.2% at a cut-off of 0.2 in cats and 0.4 in dogs, respectively)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To determine if proteinuria is more common in dogs with lymphoma when compared with healthy dogs and to assess the severity and frequency of proteinuria in dogs with lymphoma., Methods: Determination of urine protein:creatinine ratio in 32 dogs with lymphoma compared with 30 healthy dogs., Results: Canine patients with lymphoma are more likely to be proteinuric compared with healthy dogs. Proteinuria is common in dogs with lymphoma, although in most cases it is not severe. The presence of proteinuria is not linked with the stage or substage of lymphoma., Clinical Significance: Mild proteinuria is a common finding in dogs with lymphoma. The clinical impact of the proteinuria is probably low., (© 2012 British Small Animal Veterinary Association.)

Background: Physiologic peculiarities of Greyhounds as compared to other dogs make interpretation of laboratory results in this breed challenging for veterinarians. Hypertension in retired racing Greyhounds (RRG) can contribute to microalbuminuria (MA), overt proteinuria, and renal histologic lesions., Objectives: To evaluate clinicopathologic findings, hemodynamic status, and renal histology in a population of healthy RRG., Animals: RRG presented to Ohio State University College of Veterinary Medicine for inclusion in a spay and neuter program., Methods: Cross-sectional study. RRG were classified as normotensive (<160 mmHg) or hypertensive (>160 mmHg) based on blood pressure (BP) determinations using Doppler and oscillometric methods. Of the dogs evaluated, 62% (n = 29) were hypertensive and 38% (n = 18) were normotensive. Health status was evaluated using routine clinicopathologic tests (CBC, serum biochemistry, urinalysis) as well as evaluation of fractional excretion of electrolytes and MA determinations. Adequate renal biopsy specimens (n = 15) were evaluated using light, immunofluoresence, and electron microscopy., Results: All serum biochemistry results were normal in 45/49 dogs, but MA was more common in hypertensive (84% positive for MA) as compared with normotensive (18% positive for MA) RRG. Observed renal lesions were mild and renal biopsy scores were low in this sample of RRG., Conclusions: Hypertension is common in RRG and might be breed-related. It is associated with MA, but observed renal lesions are mild. Whether or not hypertension and MA in RRG leads to progressive renal damage requires longitudinal study., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Objective: To determine whether preanalytic and analytic factors affect evaluation of the urinary protein-to-creatinine (UPC) ratio in dogs., Sample: 50 canine urine samples., Procedures: The UPC ratio was measured to assess the intra-assay imprecision (20 measurements within a single session), the influence of predilution (1:10, 1:20, and 1:100) for urine creatinine concentration measurement, and the effect of storage at room temperature (approx 20°C), 4°C, and -20°C., Results: The coefficient of variation at room temperature determined with the 1:20 predilution was < 10.0%, with the highest coefficients of variation found in samples with a low protein concentration or low urine specific gravity. This variability could result in misclassification of samples with UPC ratios close to the thresholds defined by the International Renal Interest Society to classify dogs as nonproteinuric (0.2), borderline proteinuric (0.21 to 0.50), or proteinuric (> 0.51). A proportional bias was found in samples prediluted 1:10, compared with samples prediluted 1:20 or 1:100. At room temperature, the UPC ratio did not significantly increase after 2 and 4 hours. After 12 hours at room temperature and at 4°C, the UPC ratio significantly increased. The UPC ratio did not significantly change during 3 months of storage at -20°C., Conclusions and Clinical Relevance: The intra-assay precision of the UPC ratio was sufficiently low to avoid misclassification of samples, except for values close to 0.2 or 0.5. The optimal predilution ratio for urine creatinine concentration measurement was 1:20. A 1:100 predilution is recommended in samples with a urine specific gravity > 1.030. The UPC ratio must be measured as soon as samples are collected. Alternatively, samples should be immediately frozen to increase their stability and minimize the risk of misclassification of proteinuria.

Background: Proteinuria is an established characteristic of renal disease in dogs, providing diagnostic and prognostic information. Little is known about the occurrence and severity of proteinuria in dogs with severe inflammatory response syndrome (SIRS)., Hypothesis: The quantitative and qualitative urinary protein (UP) excretion is altered in dogs with SIRS., Animals: Thirty-nine dogs with SIRS and 15 healthy control dogs at admission., Methods: A case control study was performed. Diagnosis of SIRS was based on clinical and clinicopathological findings. Urinary protein (UP) was measured by a colorimetric assay. Urinary albumin (UAlb) and urinary retinol-binding protein (URBP) were measured by ELISA and quantified in relation to urinary creatinine (UC). Sodium dodecyl sulfate polyacrylamid-gel electrophoresis was conducted to identify the qualitative pattern of proteinuria. Mann-Whitney U-test was used to assess differences in UP/UC, UAlb/UC and URBP/UC between the groups. P-values < .05 were considered significant., Results: Dogs with SIRS had higher ratios of UP/UC, UAlb/UC and URBP/UC (all P < .001) in comparison to healthy control dogs. Dogs with SIRS had a total of 11 protein bands compared to 3 bands in healthy controls. In dogs with SIRS, 58% of the total counted bands were in the low molecular weight range (<60 kDa) whereas 42% were in the middle (60-80 kDa)/high molecular weight range (>80 kDa)., Conclusions and Clinical Importance: SIRS alters UP excretion in dogs. Further studies should evaluate whether or not the magnitude of proteinuria is predictive of the severity and outcome of dogs with SIRS., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

Proteinuria is a general term that describes the presence of any type of protein in the urine (e.g., albumin, globulins, mucoproteins, and Bence-Jones proteins); however, albumin is the predominate protein in urine in healthy dogs and cats as well as dogs and cats with renal disease. Proteinuria can arise from several different physiologic and pathologic causes, but persistent proteinuria associated with normal urine sediment is consistent with kidney disease. The urine dipstick colorimetric test is the usual first-line screening test for the detection of proteinuria, but false-positive reactions are common. When proteinuria of renal origin is suspected, the next diagnostic steps are quantitation and longitudinal monitoring via the urine protein/creatinine ratio. The recent availability of a species-specific albumin enzyme-linked immunosorbent assay technology that enables detection of low concentrations of canine and feline albuminuria has both increased diagnostic capability and stimulated discussion about what level of proteinuria/albuminuria is normal. Beyond being an important diagnostic marker, proteinuria is associated with kidney disease progression in both dogs and cats: the greater the magnitude of the proteinuria, the greater the risk of renal disease progression and mortality. Treatments that have attenuated proteinuria in dogs and cats have also been associated with slowed kidney disease progression and/or improved survival. For these reasons, screening for renal proteinuria and longitudinal assessment of renal proteinuria has recently received renewed interest., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aims of the current study were to assess whether sodium dodecyl sulphate-agarose gel electrophoresis (SDS-AGE) and high-resolution electrophoresis (HRE) can identify dogs with a urinary protein-to-creatinine ratio (UPC ratio) >0.2 and whether HRE can provide preliminary information about the type of proteinuria, using SDS-AGE as a reference method. HRE and SDS-AGE were conducted on 87 urine samples classified according to the International Renal Interest Society as non-proteinuric (NP; UPC ratio: <0.20; 32/87), borderline proteinuric (BP; UPC ratio: 0.21-0.50; 15/87), or proteinuric (P; UPC ratio: >0.51; 40/87). SDS-AGE and HRE were positive in 14 out of 32 and 3 out of 32 NP samples and in 52 out of 55 and 40 out of 55 samples with a UPC ratio >0.20, respectively. The concordance between HRE or SDS and UPC ratio was comparable (κ = 0.59; κ = 0.55). However, specificity (90%) and positive likelihood ratio (7.76) were higher for HRE than for SDS-AGE (56% and 2.16) while sensitivity was lower (73% vs. 94%). The analysis of HRE results revealed that a percentage of albumin >41.4% and an albumin/α(1)-globulin ratio (alb/α(1) ratio) >1.46 can identify samples classified by SDS-AGE as affected by glomerular proteinuria while a percentage of α(1)-globulin >40.8% and an alb/α(1) ratio <0.84 can identify samples classified by SDS-AGE as affected by tubular proteinuria. In conclusion, both SDS-AGE and HRE could misclassify samples with a UPC ratio higher or lower than 0.20. Therefore, UPC ratio must always be determined before conducting these tests. The percentage of albumin and α(1)-globulin or the alb/α(1) ratio determined by HRE can provide preliminary information about the origin of proteinuria.

Objective: To assess whether urine protein-to-creatinine (UPC) ratios determined in urine samples collected by cystocentesis versus those collected by free catch provide similar diagnostic information for dogs., Design: Evaluation study., Animals: 115 client-owned dogs evaluated because of various health problems requiring urinalysis or to screen for proteinuria in an area endemic for leishmaniasis., Procedures: 230 paired urine samples, 1 collected by cystocentesis and 1 by free catch, were collected from the 115 dogs. The UPC ratio was determined in paired urine samples (n = 162) from 81 dogs with no indication of active inflammation according to urine sediment analysis. On the basis of the UPC ratio of urine sample collected by cystocentesis, dogs were classified as nonproteinuric (UPC ratio < 0.2), borderline proteinuric (UPC ratio of 0.2 to 0.5), or proteinuric (UPC ratio > 0.5), according to the International Renal Interest Society (IRIS)., Results: The correlation between UPC ratio in urine samples collected by cystocentesis and by free catch was strong (r(2) = 0.90); 75 of 81 (92.6%) dogs had UPC ratios from both urine samples that resulted in classification in the same IRIS substage with a kappa coefficient of 0.83., Conclusions and Clinical Relevance: The UPC ratio in dogs was minimally affected in urine samples collected by free catch, thus allowing correct grading of proteinuria with this method. The high reliability of the UPC ratio in free-catch urine samples coupled with the ease of collection should increase the use of this value for assessment of proteinuria.

Background: Evaluation of serial urine protein:creatinine (UPC) ratios is important in prognosticating chronic kidney disease and monitoring response to therapeutic interventions. Owing to random biologic variation in dogs with stable glomerular proteinuria, multiple determinations of UPC ratios often are recommended to reliably assess urine protein loss. This can be cost-prohibitive., Objective: The purpose of this study was to evaluate agreement between the mean of 3 UPC ratios obtained on 3 separate urine samples per dog and a single UPC ratio obtained when aliquots of the separate samples were pooled and analyzed as 1 sample., Methods: Three separate urine samples were collected from each of 25 dogs, both client-owned and members of a research colony. Protein and creatinine concentrations were measured in the supernatant of each sample using a biochemical analyzer, and the mean of the 3 UPC ratios was calculated. A 1.0 mL aliquot of each of the 3 samples from each dog was pooled to create a fourth sample for that dog, and the UPC ratio of the pooled sample was similarly determined. Agreement and correlation between the mean and pooled UPC ratios were assessed using Bland-Altman difference plots and regression analysis, respectively., Results: The UPC ratio in the pooled samples was highly correlated (r=.9998, P<.0001) with the mean UPC ratio of the 3 separate samples. Strong agreement between results was demonstrated; a UPC ratio from a pooled sample was at most +/-20% different than the mean UPC ratio obtained from 3 separate samples., Conclusions: Measuring the UPC ratio in a pooled sample containing equal volumes of several different urine specimens from the same dog provides a reliable and cost-effective alternative to assessing multiple UPC ratios on several specimens from the same dog.

Bernese Mountain dogs (BMDs) are prone to develop a familial glomerulonephropathy and a pathogenic role of Borrelia burgdorferi sensu lato in this disease has been suspected. Glomerular disease in many affected dogs is clinically inapparent and proteinuria is found incidentally. In this study, urine protein excretion was evaluated in 122 clinically healthy BMDs and 55 controls. The seroprevalence of B. burgdorferi in BMDs was 57%, compared to 16% in controls. There were no significant differences in the occurrence of positive dipstick results, microalbuminuria, urine protein-to-urine creatinine ratio or abnormal urine protein pattern (determined by sodium dodecyl sulphate agarose gel electrophoresis) between BMDs and controls and BMDs with and without antibodies against B. burgdorferi. It was concluded that antibodies against B. burgdorferi are not associated with proteinuria as an early sign of renal disease in BMDs.

The clinical utility of the urine albumin/creatinine ratio (UAC) using a simplified analyzer for estimation of proteinuria was studied in cats and dogs. Measurement results for diluted feline and canine albumin standard solutions showed linearity. Although conversion formulas (y=1.28x+1.04 and y=1.67x+10.47 for cats and dogs, respectively) were necessary, urine albumin concentrations could be determined in both animals. In cats and dogs with proteinuria, the UAC changed parallel with the urine protein/ creatinine ratio (UPC), and the Log UAC and Log UPC were significantly correlated (r=0.803 (p<0.01) in cats, r=0.801 (p<0.01) in dogs). The UAC using an UAC analyzer could be used clinically as one of the basic in-hospital laboratory tests for estimation of proteinuria in cats and dogs.

Background: Interpretation of serial urine protein:creatinine (UPC) values is confounded by a lack of data regarding random biologic variation of UPC values in dogs with stable glomerular proteinuria., Hypothesis: That there is minimal day-to-day variability in the UPC of dogs with unchanging proteinuria and the number of measurements needed to reliably estimate UPC varies with the magnitude of proteinuria., Animals: Forty-eight heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) causing stable proteinuria., Methods: Urine samples were obtained daily by cystocentesis for 3 consecutive days on 183 occasions (549 samples). The UPC was measured for each sample with a single dry-film chemistry auto-analyzer. Data were analyzed retrospectively by a power of the mean model because the variance of UPC values within the 3-day evaluation periods increased as the magnitude of proteinuria increased., Results: To demonstrate a significant difference (P < .05) between serial values in these proteinuric dogs, the UPC must change by at least 35% at high UPC values (near 12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably estimate the UPC when UPC <4, but 2-5 determinations are necessary at higher UPC values., Conclusions and Clinical Importance: These guidelines for interpretation of serial UPC values in female dogs with XLHN may also be helpful for interpretation of UPC values in dogs with other glomerulopathies.

Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats.

Background: Urine protein: urine creatinine (UP:UC) ratio determined from the quantitative measurement of protein and creatinine in a single urine sample is the best feasible assessment of clinically significant proteinuria in dogs and cats. A dipstick that measures urine protein, urine creatinine, and UP:UC ratio has been used in human medicine and could have application for veterinary practice., Objective: The objective of this study was to compare the Multistix PRO dipstick (Bayer Corporation, Elkhart, IN, USA) to other biochemical methods for determination of urine protein and creatinine, and UP:UC ratio in canine and feline urine., Methods: A complete urinalysis, including sulfosalicylic acid (SSA) precipitation, was performed on urine samples submitted to our laboratory between February and April 2003 from 100 dogs and 49 cats. Urine protein and creatinine concentrations were determined by the Multistix PRO dipstick using a Clinitek 50 analyzer (Bayer) and compared with the results of SSA precipitation and quantitative biochemical analysis. The UP:UC ratios from the dipstick results (calculated by the Clinitek 50 and also manually) were compared with those calculated from quantitative values. Pearson product-moment correlation analysis and diagnostic sensitivity and specificity (using quantitative results as the gold standard) were determined., Results: For both canine and feline urine, protein and creatinine concentrations determined by the Multistix PRO correlated closely with quantitative concentrations for protein (dogs r = .78, P = .0001; cats r = .87, P = .0001) and creatinine (dogs r = .78, P = .0001; cats r = .76, P = .0001). The Multistix PRO was more sensitive and less specific than SSA precipitation for diagnosing clinically significant proteinuria. UP:UC ratios obtained by manual calculation of dipstick results correlated best with quantitative UP:UC ratios in dogs, and had higher specificity but lower sensitivity for the diagnosis of proteinuria. In cats, UP:UC ratios determined by the dipstick method did not correlate (r = -.24, P = .0974) with quantitative values., Conclusions: The Multistix PRO, with manual calculation of UP:UC, may be a good alternative for the diagnosis of clinically significant proteinuria in dogs, but not cats. Dipstick creatinine concentration should be considered as an estimate.

Samples of urine and serum from 45 newborn rottweiler puppies from six litters, and milk from their mothers, were taken 24, 48 and 72 hours and seven and 14 days after birth. Urine total protein and creatinine concentrations were determined and the ratios calculated. The immunoglobulin (Ig) concentrations of IgG, IgM and IgA in urine, serum and milk were determined with a commercially available elisa kit. The concentration of total protein in urine decreased from 1.64 to 0.29 mg/ml, and it and the ratio of total protein to creatinine in the urine of the neonatal puppies exceeded the normal values for adult dogs, but all the puppies developed normally. The average concentration of IgG in urine decreased from 0.0035 to 0.0003 mg/ml, that of IgA from 0.0035 to 0.0002 mg/ml and that of IgM from 0.0006 mg/ml to undetectable levels after two weeks. After two weeks, 47 per cent of the puppies had measurable levels of IgA and 70.6 per cent had measurable levels of IgG, but none of them had measurable levels of IgM.

Objective: To determine whether urine protein-to-creatinine ratio (UP:C) > or = 1.0 at initial diagnosis of chronic renal failure (CRF) is associated with greater risk of development of uremic crises, death, and progression of renal failure in dogs., Design: Prospective cohort study., Animals: 45 dogs with CRF PROCEDURE: Dogs were prospectively assigned to 2 groups on the basis of initial UP:C < 1.0 or 2 > or = 1.0. The association between magnitude of proteinuria and development of uremic crises and death was determined before and after dogs with initial UP:C > or =1.0 were assigned to 3 subgroups and compared with dogs with initial UP:C < 1.0. Changes in reciprocal serum creatinine concentration were used to estimate decrease in renal function., Results: Initially, dogs had similar clinical characteristics with the exception of systolic blood pressure and UP:C. Relative risks of development of uremic crises and death were approximately 3 times higher in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0. Relative risk of adverse outcome was approximately 1.5 times higher for every 1-unit increment in UP:C. The decrease in renal function was of greater magnitude in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0., Conclusions and Clinical Relevance: Initial UP:C > or =1.0 in dogs with CRF was associated with greater risk of development of uremic crises and death, compared with dogs with UP:C < 1.0. Initial determinations of UP:C in dogs with naturally occurring CRF may be of value in refining prognoses.

The purpose of this retrospective study was to investigate the relationship among proteinuria consisting of immunoglobulin free light chains (FLCs), renal histopathologic findings, and routine markers of renal function in 11 dogs exposed to Leishmania infantum (n = 8), Ehrlichia canis (n = 2), and Babesia canis (n = 1). FLC proteinuria was suspected based on identification of a 22- to 27-kDa band by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and later confirmed by immunofixation electrophoresis. SDS-AGE identified an isolated band of 22-27 kDa in 8 dogs, whereas the remaining 3 had a 22- to 27-kDa band and an additional band of 67-72 kDa. The median urine protein-to-urine creatinine ratio was 0.37 (range, 0.11-2.24) and increased ratios were found in 6 dogs (54.5%) (reference value, <0.7). All dogs underwent histologic examination of renal percutaneous biopsy specimens and determination of serum creatinine and urea concentrations. Tissue samples for light microscopy were stained with hematoxylin-eosin, periodic acid-Schiff, Goldners trichrome, and methenamine silver. In the study group, the glomerular tufts, mesangium, tubulointerstitium, and vessels appeared unaffected. The median serum creatinine concentration in these 11 dogs was 1.3 mg/dL (range, 0.8-1.5 mg/dL; reference range, 0.6-1.5 mg/dL), whereas the concentration for urea was 28 mg/dL (range, 22-52 mg/dL; reference range, 20-50 mg/dL). All dogs had normal renal morphology and had normal serum creatinine and urea concentrations, suggesting that immunoglobulin FLC may be detected in the urine of dogs exposed to L. infantum, E. canis, and B. canis without any apparent structural or functional renal derangement.

Canine pyometra often causes glomerulonephritis by immune complex deposition in the glomeruli. Proteinuria, ranging from moderate to severe, may be present secondary to renal damage. To determine urinary protein excretion due to pyometra, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was conducted on urine from 15 bitches with pyometra and 10 healthy bitches. To characterize urinary immunoglobin excretion, Western blot analysis of the urine samples using antibodies to canine IgG and IgA was also performed. Nine bands were detected by electrophoresis in bitches with pyometra, while only four were detected in the healthy animals. The urinary proteins from bitches with pyometra were primarily of glomerular origin; 58% were of medium-high molecular weight (MW), and the remainder were low MW. None of the healthy dogs had IgG or IgA in their urine, whereas three bitches with pyometra had IgG in their urine and another bitch with pyometra had both IgG and IgA. The low proportion of bitches with urinary immunoglobins was probably be due to early diagnosis of the disease. Although only a limited number of dogs was used, this study is apparently the first to characterize the electrophoretic pattern of urinary proteins and to quantify urinary excretion of IgG and IgA in bitches with pyometra.

Objective: To evaluate urine protein content in dogs with pituitary-dependent hyperadrenocorticism (PDHAC) and to determine the effect of mitotane administration on proteinuria in these dogs., Design: Prospective case series., Animals: 16 dogs with PDHAC were evaluated (age range, 7 to 14 years; mean age, 10 years; female-to-male ratio, 2.2:1)., Procedure: Urine protein-to-creatinine (UPC) ratios and 24-hour urine protein excretion (24-hour UPE) values were measured before beginning treatment with mitotane and after establishing appropriate maintenance treatment., Results: Before treatment, UPC ratios ranged from 0.03 to 4.16 (16 dogs, median, 0.695; reference range value, UPC ratio < 0.5; questionable value, UPC ratio > 0.5 but < 1.0; high value, UPC ratio > 1.0). Seven dogs had proteinuria with UPC ratios > 1.0. Twenty-four-hour UPE values ranged from 0.67 to 61.7 mg/kg of body weight/d (0.30 to 28.0 mg/lb/d; 13 dogs, median, 9.7 mg/kg/d [4.4 mg/lb/d]; reference value, 24-hour UPE value, < 20 mg/kg/d [9.1 mg/lb/d]). Five dogs with high UPC ratios also had high values for 24-hour UPE. After establishment of maintenance treatment with mitotane (median, 7 weeks; mean, 7.3 weeks), UPC ratios ranged from 0.02 to 6.5 (16 dogs, median, 0.36). Five dogs continued to have high UPC ratios. Values of 24-hour UPE ranged from 0.47 to 122 mg/kg/d (0.21 to 55.5 mg/lb/d; 13 dogs, median, 5.1 mg/kg/d [2.3 mg/lb/d]). Three dogs continued to have high 24-hour UPE values. Significant differences were not found between dogs before and after treatment with mitotane in terms of UPC ratios or 24-hour UPE values., Clinical Implications: In dogs with PDHAC and proteinuria, UPC ratios should be monitored closely. Some dogs with PDHAC may have a decrease in urine protein content following treatment with mitotane. We suggest that renal biopsies be considered in those dogs with progressive increases in UPC ratios.

Objective: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease., Design: Case series and cohort study., Animals: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment., Results: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease., Clinical Implications: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.

Dogs with spontaneous Diabetes mellitus were checked at regular intervals for protein excretion in the urine. A large number of dogs developed a proteinuria, very marked in some cases, with excretion of primarily macroproteins.

Urinary protein-to-creatinine ratios and serum albumin concentrations were measured in 8 adult male dogs experimentally inoculated with Ehrlichia canis. Urinary protein concentration increased significantly, but transiently, during the acute phase of infection. Urinary protein-to-creatinine ratios were highest (mean, 8.6) during the third and fourth weeks after infection, and decreased to less than 0.5 by 6 weeks after infection. Correspondingly, albumin concentration decreased significantly during the acute phase. Serum albumin concentrations were lowest (mean, 2.1 g/dl) the fourth week after infection and increased to greater than 3.0 g/dl by 11 weeks after infection. There was an inverse linear correlation between urinary protein-to-creatinine ratio and serum albumin concentration. The magnitude of proteinuria and its inverse relationship with serum albumin concentration suggested that hypoalbuminemia associated with acute E canis infection may be attributable primarily to increased renal loss of protein, rather than decreased hepatic synthesis as previously suggested. Another dog was subsequently inoculated with E canis from 1 of the experimentally infected dogs and a renal biopsy was performed during peak proteinuria (urinary protein-to-creatinine ratio = 22 and serum albumin = 1.1 g/dl). Immunofluorescent staining revealed mild to moderate deposits of anti-canine IgM, and to a lesser extent, anti-canine IgG and complement factor C3 in the glomerular tufts and mesangium. Ultrastructural evaluation revealed distortion and fusion of podocyte foot processes and increased microvilli on podocytes. These morphologic changes were consistent with transient glomerular leakage of protein of a magnitude that would significantly contribute to hypoalbuminemia during acute E canis infection. An underlying immunologic mechanism was suggested by positive glomerular immunofluorescence and previously described histologic findings.

The effect of experimentally induced cystitis and iatrogenic blood contamination on the urine protein/creatinine ratio (U P/C) was evaluated in 17 dogs. Before they were included in the study, all dogs were judged to be healthy on the basis of physical examination, serum concentrations of urea nitrogen and creatinine, complete urinalysis, and a U P/C less than 0.4. A single urine sample was contaminated with increasing quantities of canine fresh whole blood (PCV = 42%; total protein = 6.2 g/dl). When added blood was equal to or greater than 25% of the total urine sample volume, the U P/C exceeded 3.5, a finding consistent with nephrotic range proteinuria. When added blood was 10% of the total urine sample volume, the U P/C was less than 1.8. Eleven Beagles underwent routine laparotomy during which a cystotomy was done. The median U P/Cs on postoperative days 1 and 2 were significantly increased compared with preoperative values (P less than 0.05); no U P/C exceeded 2.0. Renal biopsies performed on postoperative day 3 eliminated renal proteinuria as a source of urine protein. Five dogs had bacterial cystitis experimentally induced. At 72 and 96 hours after bacterial inoculation, the median U P/Cs were significantly increased (P less than 0.05); individual values ranged from 1.5 to 40.8. Renal biopsies performed between 5 and 6 days after inoculation eliminated renal proteinuria as a source of urine protein. Cytologic evaluation of urine sediment in each group did not correlate with the magnitude of the increase in the U P/C. The U P/C significantly increased in each model of lower urinary tract inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)