Renal amyloid-A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology.

BACKGROUND: Amyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria. OBJECTIVES: Investigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis. ANIMALS: Twenty-nine shelter cats. METHODS: Case-control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed. RESULTS: Twenty-nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6-12.7 vs 1.5; 0.6-3.1; P = .03) and UAAC ratios (median, 7.18 × 10-3 ; range, 23 × 10-3 -21.29 × 10-3 vs 1.26 × 10-3 ; 0.21 × 10-3 -6.33 × 10-3 ; P = .04) than unaffected cats. The SDS-AGE identified mixed-type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC-MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C-III was higher in cats with AA amyloidosis (median, 1.38 × 107 ; range, 1.85 × 105 -5.29 × 107 vs 1.76 × 106 ; 0.0 × 100 -1.38 × 107 ; P = .01). In the kidney, AA-amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Renal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.

The relationships between sediment findings and culture results and the presence of proteinuria in canine urine samples.

OBJECTIVES: To assess relationships between urine sediment and microbial culture findings and the presence of proteinuria in canine urine samples, and to assess the change in the percentage of proteinuric samples and urine protein-to-creatinine ratio when urine abnormalities resolve. MATERIALS AND METHODS: Canine urine samples collected via cystocentesis and submitted for culture and contemporaneous urinalysis (including urine protein-to-creatinine ratio) were retrospectively identified. Dogs receiving corticosteroids were excluded. Associations between haematuria (red blood cells>5/high-power field), pyuria (white blood cells>5/high-power field), presence of microorganisms on microscopy, active sediment, and positive culture and proteinuria (urine protein-to-creatinine ratio>0.5) were investigated. Patient characteristics were considered possible confounders. In dogs with repeat urinalysis, the associations between active sediment and positive culture resolution on proteinuria and urine protein-to-creatinine ratio were assessed. RESULTS: One hundred and ninety-two of 491 samples were proteinuric (39.1%). Age was positively associated with proteinuria. In the multivariable analysis corrected for age, active sediment was the only variable significantly associated with proteinuria (adjusted odds ratio: 2.12; 95% confidence interval: 1.44 to 3.11); however, only 49.8% of samples with active sediment were proteinuric. Neither resolution of active sediment nor positive culture were associated with reduced proportions of proteinuric samples (from 57.9% to 42.1% and from 40.0% to 25.0%, respectively) or significant reductions in urine protein-to-creatinine ratio (median change: -0.16 and -0.14, respectively). CLINICAL SIGNIFICANCE: Attributing proteinuria to urinalysis abnormalities or a positive urine culture in canine cystocentesis samples is not supported by our findings, and could result in alternative causes of proteinuria (e.g. renal proteinuria) being overlooked.

Comparison of cystocentesis versus home sampling to determine urinary protein: Creatinine ratio and urine specific gravity in cats.

BACKGROUND: Urinalysis is necessary for the diagnostic evaluation of chronic kidney disease in cats. Performing cystocentesis is not always feasible, but data comparing urine obtained by cystocentesis in the clinic with voided samples collected at home are lacking in cats. OBJECTIVES: To compare urinary protein:creatinine ratio (UPC) and urine specific gravity (USG) and to detect clinically relevant changes in proteinuria substage or urine concentration between urine collected at home and in-clinic by cystocentesis in cats. ANIMALS: Ninety-two healthy and diseased client-owned cats. METHODS: Prospective study. Owners collected voided urine at home and within 1 to 15 hours, cystocentesis was performed in the clinic. RESULTS: In a subset of motivated owners, 55% succeeded in collecting urine at home. Overall, UPC was higher (mean ±SD difference = 0.09 ±0.22; P < .001) and USG was lower (mean ±SD difference = -0.006 ±0.009; P < .001) in cystocentesis samples than in voided urine. Substantial agreement existed between sampling methods for UPC (weighted к = 0.68) and USG (к = 0.64) categories. A different proteinuria substage (UPC < 0.2, 0.2-0.4, >0.4) was present in paired urine samples from 28% of cats. In 18% of cats, urine concentrating ability (USG < or ≥1.035) differed between both samples. CONCLUSIONS AND CLINICAL IMPORTANCE: Home sampling of urine is a valid alternative to cystocentesis in cats. However, because clinically relevant differences in UPC and USG were present in 28% and 18% of cats, respectively, by the same collection method for monitoring each cat is advised.

Cross-sectional characterization of renal function in cats with caudal stomatitis.

OBJECTIVES: The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats. METHODS: A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a t-test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test. RESULTS: Relative to the control group, cats in the CS group had significantly lower serum creatinine (P <0.001) and albumin concentrations (P <0.001), urine specific gravity (P = 0.024) and hematocrit (P = 0.003), and higher serum phosphorus (P <0.001), potassium (P <0.001) and globulin concentrations (P <0.001), white blood cell count (P <0.001) and urine protein:creatinine ratio (P = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups. CONCLUSIONS AND RELEVANCE: The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.

Mycophenolate mofetil and telmisartan for the treatment of proteinuria secondary to minimal change disease podocytopathy in a dog.

A 3-year-old entire female Springer Spaniel, with a previous diagnosis of meningoencephalitis of unknown origin diagnosed 2 years before presentation and treated with long term administration of prednisolone, developed proteinuria. Laboratory findings revealed hypoalbuminemia, hypercholesterolemia, and proteinuria. Further investigations excluded underlying causes. Renal biopsies were performed. The glomeruli and the tubulointerstitial compartment did not show any anomalies on light microscopy and immunofluorescence staining did not reveal abnormalities. Transmission electron microscopy revealed moderate podocyte injury consisting of foot process effacement and microvillus transformation of the cytoplasm. The dog was diagnosed with primary minimal change disease of the podocytes and treated with telmisartan and mycophenolate mofetil. Abnormalities of serum albumin, cholesterol, and proteinuria resolved within 4 weeks. Minimal change disease has been reported in dogs, but this is a case report of proteinuria secondary to minimal change disease successfully treated with mycophenolate mofetil and telmisartan.

Spurious laboratory results associated with immunoglobulin M gammopathy in a dog with multiple myeloma.

An 11 year old female-neutered Labrador presented for facial swelling. Clinicopathological abnormalities included hyperglobulinemia, azotemia, hypercalcemia, nonregenerative anemia, thrombocytopenia, and spurious hypoglycemia. Normoglycemia was subsequently confirmed using a cage-side analyzer (AlphaTRAK, Zoetis, UK). Serum and urine protein electrophoresis documented monoclonal (immunoglobulin M) gammopathy with Bence-Jones proteinuria. Computed tomography imaging revealed a monostotic osteolytic bone-lesion, and bone marrow cytology and histopathology documented plasmacytosis with multiple myeloma oncogene 1 / interferon regulatory factor 4 positivity, consistent with multiple myeloma. Infectious disease testing initially indicated seropositivity for Leishmania, Borrelia, and Anaplasma spp.; however, Leishmania PCR (splenic and bone marrow aspirates), and paired serological titers for Borrelia and Anaplasma were negative. Consequently, initial serological results were considered to be false positive because of paraproteinemia-associated assay interference. Chemotherapy (prednisolone and melphalan combination therapy) was initiated, but the dog was euthanased 30 days later because of the development of pericardial effusion. This is a report of spurious serological (and other laboratory) results occurring secondary to monoclonal gammopathy in a dog.

Establishment of a reference interval for urinary albumin-to-creatinine ratio in dogs.

BACKGROUND: Albuminuria is an important marker of renal damage and can precede proteinuria; thus, it can be a useful analyte in the early diagnosis of kidney diseases. Albuminuria has also been found in dogs with hypertension, inflammatory, infectious, and neoplastic diseases. OBJECTIVES: The aim of this study was to establish a reference interval (RI) for albuminuria in dogs. METHODS: One hundred sixty-four clinically healthy dogs were enrolled in the study. Urinary albumin was determined by the immunoturbidimetric method, and albumin excretion was expressed as the urinary albumin-to-creatinine (UAC) ratio. The RI for UAC was established. RESULTS: After exclusions, 124 dogs from 32 breeds remained. The median UAC of the study population was 3.0 mg/g (range: 0-48). The RI was defined as 0-19 mg/g (with a 90% CI for the upper limit of 13-28 mg/g). No significant difference was found between male and female dogs or between different age and body weight groups. The results of Sighthounds (n = 30) and Beagle dogs (n = 23) did not differ from the other breeds. CONCLUSION: The canine RI of UAC is similar but somewhat narrower than the human RI.

The effect of non-absorbent hydrophobic sand litter on the urine protein-to-creatinine ratio in feline urine.

BACKGROUND: Proteinuria can be quantified through the measurement of the urine protein-to-creatinine ratio (UPC). Voided urine samples in cats are often exposed to a non-absorbable litter substrate prior to collection and urinalysis. Little is known about the effect exposure to such substrates has on pre-analytical variability of UPC measurements. OBJECTIVES: The aim of this study was to assess agreement between UPC measurements from urine obtained by cystocentesis before and after exposure to non-absorbent hydrophobic sand for 24 hours. METHODS: UPCs were measured in 40 urine samples obtained by cystocentesis from 39 cats (baselineUPC). Urine was then exposed to non-absorbent hydrophobic sand litter for 24 hours, recovered, and repeat UPCs were measured (litterUPC). Agreement between paired measurements and the presence of any bias or error was evaluated using Bland-Altman analysis Passing-Bablok regression analysis, respectively. Cohen's kappa was used to measure agreement for the International Renal Interest Society (IRIS) proteinuria classification of samples. Observed total error (TEobs ) was calculated for the laboratory analyzer and compared against absolute percentage changes in paired UPC measurements. RESULTS: Neither proportional nor constant error was identified using Passing-Bablok regression between baselineUPC and litterUPC. Visual inspection of the Bland-Altman plot revealed good agreement, with 95% of paired measures falling within the limits of agreement (LOA). Cohen's kappa demonstrated almost perfect agreement for the IRIS classification of proteinuria between baselineUPC and litterUPC. Absolute percentage changes of paired UPC measurements outside of the LOAs were lower than the inter-assay TEobs . CONCLUSIONS: Feline urine exposed to non-absorbent hydrophobic sand litter appears acceptable for UPC measurements.

Urinary bladder wall mass with neoplastic lymphoid cells in the urine: Diagnosis of an IgG secretory B-cell lymphoma with Bence-Jones proteinuria in a dog.

In this study, we describe a multimodal approach to diagnose a unique case of myeloma-related disease, extranodal secretory B-cell lymphoma with urinary bladder involvement, an IgG4 monoclonal gammopathy, and Bence-Jones proteinuria in a dog with a 6-year history of hyperglobulinemia that had not been further evaluated. A 12-year-old dog was presented for evaluation of a 1-week history of tenesmus. Urine sediment cytologic evaluation revealed low to moderate numbers of intermediate to large-sized lymphocytes. We describe a technique that yielded adequate numbers of viable neoplastic cells in shipped urine sediment for PARR and flow cytometry. Those studies demonstrated a clonal immunoglobulin gene rearrangement and an expansion of CD21-positive and MHC Class II-negative B cells, respectively. Protein electrophoresis with immunofixation and proteomic evaluation revealed a serum and urine IgG4 monoclonal gammopathy with Bence-Jones proteinuria. MUM1 immunocytochemistry performed on the urine sediment slides failed to label the neoplastic cells; thus, a plasma cell tumor was considered unlikely. Lack of response to a cyclophosphamide, vincristine, and prednisone chemotherapy regimen led to euthanasia without necropsy 21 days after diagnosis. Lymphoma is the most common hematopoietic malignancy and accounts for up to a quarter of all neoplasms in dogs, but lymphoid neoplasms arising primarily from extranodal sites are infrequently reported. Urinary tract neoplasia can be diagnosed by urine evaluation in about one-third of canine cases, but the diagnosis of lymphoid neoplasia via urine evaluation is rarely reported. This case highlights the utility of ancillary diagnostics on urine for detection of lymphoid malignancies.

Does intravenous contrast medium administration result in altered renal biomarkers? A study in clinically stable cats with and without azotemia.

OBJECTIVES: The aim of this study was to determine the prevalence of post-contrast acute kidney injury or comparable side effects on kidney function in cats receiving the non-ionic, iodinated agent ioversol and/or paramagnetic agent gadoteric acid. METHODS: Fifty-two animals were divided into four groups on the basis of contrast medium administration for imaging: ioversol (n = 27), gadoteric acid (n = 12), dual contrast media (n = 4) or control, which received an infusion of isotone intravenous fluids only during anaesthesia (n = 9). Blood and urine samples were obtained three times after contrast administration and compared with values obtained prior to administration of the contrast medium. Creatinine (<1.60 mg/dl), symmetric dimethylarginine (SDMA; ⩽14 µg/dl), urine protein:creatinine ratio (UPC; <0.2) and critical differences for creatinine (<0.3 mg/dl) and SDMA (<5.98 µg/dl) were measured. RESULTS: No significant short-term effects on mean creatinine, SDMA and UPC measurements were seen. Borderline proteinuria (UPC, 0.2-0.4) was detected in 11.4% of cases after contrast media administration. A UPC of more than 0.2 in five cases indicated that contrast media may affect kidney function, leading to (transient) proteinuria. CONCLUSIONS AND RELEVANCE: This study found no side effect on renal function following the administration of ioversol or gadoteric acid, provided patients were adequately hydrated. However, the clinical relevance of proteinuria in some cats needs to be evaluated in future studies.

Familial nephropathy in Bracchi Italiani: 8 cases (2012-2019).

OBJECTIVE: To characterize the signalment, clinical signs, clinical pathological and histologic findings, and outcome in 8 related Bracchi Italiani with proteinuric kidney disease. ANIMALS: 8 client-owned Bracchi Italiani. PROCEDURES: Health records submitted to the Bracco Italiano Health Foundation and the Bracco Italiano Club of America between 2012 and 2019 were reviewed for dogs with evidence of nephropathy for which histologic diagnoses were obtained. Pedigree, signalment, clinical signs, diagnostic test results (including microscopic examination of kidney tissue samples collected ante- or postmortem), and outcome were acquired. Results were presented as descriptive statistics. RESULTS: The most common clinical sign in affected dogs was inappetence. All dogs were proteinuric, and 4 dogs were azotemic. Seven dogs developed clinical signs of kidney disease and were euthanized a median of 75 days postdiagnosis. Six dogs had glomerular amyloidosis, and 1 dog each had nephrosclerosis and nonamyloidotic fibrillar glomerulopathy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the clinical presentation may vary in affected dogs, and proteinuria in young or middle-aged Bracchi Italiani should raise the concern for hereditary nephropathy. Prognosis is likely poor once clinical signs are noted.

Development and progression of proteinuria in dogs treated with masitinib for neoplasia: 28 cases (2010-2019).

OBJECTIVES: To describe the incidence, severity and progression of proteinuria over the first 6 months of masitinib treatment in tumour-bearing dogs without pre-existing proteinuria. To describe the effect of treatment on urine protein:creatinine and renal parameters in patients with pre-existing proteinuria. MATERIALS AND METHODS: Records were reviewed from patients receiving masitinib for neoplasms between June 1, 2010, and May 5, 2019. Patients without pre-treatment and at least one urine protein:creatinine after ≥7 days treatment were excluded. Signalment, tumours and concurrent diseases, treatments, haematology, biochemistry and urinalysis results before, during and after treatment for up to 202 days were collected. Patient visits were grouped into six timepoints for analysis. RESULTS: Twenty-eight dogs were included. Eighteen percent of dogs non-proteinuric at baseline (four of 22) developed proteinuria during treatment, all within 1 month of treatment initiation. One dog developed hypoalbuminaemia, none developed oedema or ascites, azotaemia or were euthanased/died due to proteinuria. Masitinib was immediately discontinued in both dogs in which urine protein:creatinine greater than 2.0 was detected and in both, proteinuria improved. Six dogs with pre-treatment proteinuria were treated with masitinib, significant worsening of proteinuria did not occur. Neither azotaemia nor severe hypoalbuminaemia occurred. CLINICAL SIGNIFICANCE: Proteinuria, when it occurs, tends to develop within 1 month of masitinib commencement and may progress rapidly. Weekly proteinuria monitoring should be considered for the first month and a urine protein:creatinine greater than 0.5 should prompt reassessment within 1 week. Masitinib treatment can be considered in patients with pre-treatment proteinuria and does not inevitably cause worsening of proteinuria.

Proteinuria in dogs with gallbladder mucocele formation: A retrospective case control study.

BACKGROUND: Proteinuria is an independent risk factor for morbidity and mortality in dogs. An association between proteinuria and gallbladder mucocele formation in dogs is unknown. OBJECTIVE: Determine if gallbladder mucocele formation or clinicopathologic comorbidities are associated with proteinuria. ANIMALS: Twenty-five dogs with mucocele formation and 25 breed and age-matched control dogs from a prior study. METHODS: Retrospective case control study. Proteinuria defined by calculated urine dipstick protein concentration (mg/mL) to urine specific gravity (USG) ratio. Clinicopathologic findings, postcosyntropin cortisol concentration, thyroid function profile, and illness severity score were recorded. RESULTS: Median urine dipstick protein concentration to USG ratio and number of dogs having a ratio ≥1.5 were significantly higher for dogs with mucocele formation compared to control dogs. Proteinuria was not significantly associated with CBC or serum biochemistry profile abnormalities but increased in relation to severity of illness. CONCLUSIONS AND CLINICAL IMPORTANCE: Gallbladder mucocele formation is significantly associated with proteinuria in dogs. Diagnosis and treatment of proteinuria in dogs with mucocele formation might minimize long term kidney morbidity in these patients.

Desempenho de diferentes marcas de tiras reagentes relativo à densidade e à análise química da urina de cães e gatos / Performance of different brands of reagent strips for density and chemical analysis of dog and cat urine

Objetivou-se verificar a compatibilidade entre diferentes marcas de tiras reagentes para urinálise, tanto de uso veterinário, como de uso humano, e confrontar os parâmetros semiquantitativos desse instrumento com métodos quantitativos. Para isso, foram analisadas 77 amostras frescas de urina de cães e gatos e testados 04 modelos de tiras reagentes. Quanto à densidade urinária, houve correlação razoável entre os métodos quantitativo e semiquantitativo naquelas amostras com pH ácido, mas não naquelas com pH neutro ou alcalino. Quanto à concentração proteica, houve similaridade de 53,3% a 83,3% entre as marcas testadas e quando comparadas com a análise fotométrica houve uma correlação razoável (rs = 0,69752 a 0,75074). Em ponto de corte de 15mg/dL de proteína, a sensibilidade da tira reagente foi 82,5% e 100% para urina canina e felina, respectivamente. No tocante à hematúria, houve divergência razoável entre a sedimentoscopia e as diferentes marcas de tiras reativas. Quanto à piúria, há uma baixa sensibilidade das tiras em relação às amostras caninas com muitos resultados falso-negativos (33% a 75%), enquanto em amostras felinas a sensibilidade foi de 100%. Assim, independente da marca, as tiras reagentes devem servir apenas como teste rápido de triagem, sendo mais apropriado o uso de métodos quantitativos na avaliação clínica do paciente a partir da urinálise.

The aim was to verify the compatibility between different brands of urinary dipsticks, for both human and veterinary use, and to compare the semiquantitative parameters of this instrument with quantitative methods. For this, 77 fresh samples of urine from dogs and cats were analyzed e and 04 models of reagent strips were tested. Regarding urinary density, a reasonable correlation was observed between the quantitative and semiquantitative methods in those samples with acidic pH, which did not occur in those with neutral or alkaline pH. Regarding the protein concentration, there was similarity from 53.3% to 83.3% between the brands and in the comparative analysis between the control strip and the photometric analysis, there was a reasonable correlation (rs = 0.69752 to 0.75074). In cut-off point of 15mg/dL protein, the sensitivity of the reagent strip was 82.5% and 100% for canine and feline urine, respectively. Regarding hematuria, there was a reasonable divergence of results between sedimentation and tested dipsticks. As for pyuria, there is a low sensitivity of the strips in relation to canine samples with many false negative results (33% to 75%), while in feline samples the sensitivity was 100%. Thus, regardless of the brands, the reagent strips should serve only as a rapid screening test, while the use of quantitative methods in the clinical evaluation of the patient from urinalysis is more appropriate.

Assessment of urinary 15-F2 -isoprostanes in dogs with urothelial carcinoma of the urinary bladder and other lower urinary tract diseases.

BACKGROUND: The 15-F2 -isoprostanes are by-products of oxidative stress and are increased in the urine of people with lower urinary tract diseases (LUTD), especially urinary neoplasia. Urothelial carcinoma (UC) is the most common urinary neoplasm in dogs. Earlier detection of UC by noninvasive means could lead to improved outcomes. Urinary 15-F2 -isoprostanes potentially could provide this means, but have not been evaluated in dogs with UC. OBJECTIVE: The objective of this study was to measure urinary 15-F2 -isoprostanes in dogs with UC and dogs with other LUTD. ANIMALS: One hundred seventeen dogs: 46 dogs with UC, 30 dogs with LUTD, and 25 control dogs. METHODS: Any dog that was presented with dysuria was eligible for inclusion. Diagnosis of UC was confirmed histologically. Urinalysis was performed in each case, and 15-F2 -isoprostanes quantified by gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) and normalized to urinary creatinine concentration. RESULTS: Dogs with urinary diseases (UC + LUTD) had higher median urinary 15-F2 -isoprostanes when compared to control dogs (5.92 ng/mg [range, 0.46-31.03] vs 3.73 [range, 1.8-7.98]; P = .02). Urinary 15-F2 -isoprostanes were similar in dogs with UC (5.33 ng/mg [range, 0.46-31.03]) compared to dogs with LUTD (6.29 ng/mg [range, 0.54-18.93]; P = .47) and control dogs (P = .06). Dogs with UC had higher qualitative measures of proteinuria (P = .004), hematuria (P = .01), and epithelial cells on urinalysis (P = .002) compared to the other groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary F2 -isoprostanes are not useful for the detection of UC in dogs. Future research could evaluate urinary 15-F2 -isoprostanes as a marker of inflammation in disease progression and prognosis.

Electrophoretic analysis (sds-page) of canine urinary proteins according to the stage of chronic kidney disease / [Análise eletroforética (SDS-PAGE) de proteínas urinárias de cães de acordo com o estágio da doença renal crônica]

Glomerular proteinuria is characterized by the loss of high-molecular-weight proteins (HMWPs), while tubulointerstitial proteinuria is characterized by the loss of low-molecular-weight proteins (LMWPs). The objective was to assess the molecular weight of urinary proteins (MWUP) in dogs with naturally acquired CKD and determine the proportion of HMWPs and LMWPs according to CKD stage. Twenty-eight dogs with CKD were recruited and divided into 4 groups based on serum creatinine (Cr) levels (group1: Cr<1,4, n=8; group2: 1,45,0, n=5). The control group consisted of 5 healthy dogs. The MWUP was determined by SDS-PAGE. The urinary protein-to-creatinine ratio (UP/C) was used to quantitatively assess proteinuria. The electrophoresis pattern revealed a proportionally greater loss of HMWPthan of LMWP in all groups with CKD and an increased loss of LMWP in group 4 (P<0.05). These results suggest a predominance of glomerular injuries throughout all stages of CKD in these dogs and an increase in tubulointerstitial injury towards the end-stage of the disease. The results of the present study support the recommendation of SDS-PAGE as an effective technique for the qualitative assessment of proteinuria, as well as a method for assessing the severity and location of renal injury.(AU)

A proteinúria glomerular é caracterizada pela perda de proteínas de alto peso molecular (PAPM), enquanto a proteinúria tubulointersticial se caracteriza pela perda de proteínas de baixo peso molecular (PBPM). O objetivo do trabalho foi determinar o peso molecular das proteínas urinárias (PMPU) de cães com DRC naturalmente adquirida e a proporção de PAPM e PBPM de acordo com o estágio da DRC. Foram utilizados 28 cães com DRC, divididos em quatro grupos, de acordo com o nível sérico de creatinina (cr) (grupo 1: cr<1,4, n=8; grupo 2: 1,45,0, n=5). O grupo controle era composto por cinco cães saudáveis. O PMPU foi determinado por SDS-PAGE. A relação proteína:creatinina urinária (RPCU) foi utilizada como um método quantitativo de proteinúria. A eletroforese revelou uma perda proporcionalmente maior de PAPM, quando comparada às PBPM, em todos os grupos de DRC, bem como uma perda crescente de PBPM no grupo 4 (P<0,05). Esses resultados sugerem uma predominância de lesão glomerular em todos os estágios de DRC nesses cães e uma progressão crescente na lesão túbulo-intersticial no estágio terminal da doença. Os resultados deste estudo reafirmam a recomendação de que a eletroforese de proteínas urinárias é uma técnica qualitativa efetiva de avaliação da proteinúria, bem como um método que permite avaliar a extensão e a localização da lesão renal.(AU)

Clinicopathologic and pathologic characteristics of feline proteinuric kidney disease.

OBJECTIVES: The aim of this study was to describe the causes, clinicopathologic features and outcomes of feline protein-losing nephropathy (proteinuria secondary to glomerular disease [PLN]). METHODS: Kidney biopsy/necropsy samples from proteinuric cats submitted to the International Veterinary Renal Pathology Service were retrospectively reviewed. Diagnoses based on histopathology were categorized by primary disease compartment. Clinicopathologic variables at diagnosis, development of hypoalbuminemia, anemia, hypertension, azotemia and effusion/edema, and survival were compared between cats with immune-complex glomerulonephritis (ICGN) and other causes of PLN. RESULTS: Fifty-eight percent (n = 31/53) of proteinuric cats had ICGN and 74% (n = 31/42) of cats with PLN had ICGN. Cats with glomerular diseases other than ICGN had a higher median urine protein:creatinine ratio than ICGN cats (14.5 vs 6.5; P <0.001). Onset of PLN occurred at a young age; median age at diagnosis was 3.5 years in ICGN cats vs 1.3 years in cats with other glomerular diseases (P = 0.026). Development of complications such as hypoalbuminemia, anemia, hypertension, azotemia and effusion/edema were common, regardless of the cause of PLN, and were not different between ICGN and cats with other glomerular diseases. Male cats were over-represented in the ICGN group (P = 0.003). Median survival time (MST) for all cats with PLN was 94 days (range 3-1848 days). Survival was not different between cats with ICGN and cats with other glomerular diseases. MST in ICGN cats that developed effusion was shorter (94 days) than cats that did not (700 days; P = 0.035). MST in IGCN cats that received immunosuppressive medications was longer (244 days) than cats that did not (17 days, P = 0.039). CONCLUSIONS AND RELEVANCE: Taken together, these data suggest that clinical suspicion for glomerular proteinuria should increase in young, male cats with higher degrees of proteinuria, and immune-mediated disease is common. Further studies are needed to determine the effect of immunosuppression on morbidity and mortality in cats with ICGN.

Thrombin generation and thromboelastometry tests in dogs with chronic kidney disease / Testes de geração de trombina e tromboelastometria em cães com doença renal crônica

Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

Characteristics associated with bacterial growth in urine in 451 proteinuric dogs (2008-2018).

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.

Clinicopathologic characteristics, pathology, and prognosis of 77 dogs with focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of nonimmune complex glomerulopathy and the prognosis and clinicopathologic findings associated with this condition have not been described in dogs. OBJECTIVE: To characterize the presentation and identify clinical factors associated with the survival of dogs with FSGS. ANIMALS: Seventy-seven dogs diagnosed with FSGS based on evaluation of renal biopsy samples submitted to the International Veterinary Renal Pathology Service. METHODS: Retrospective review of medical records of dogs biopsied for evaluation of proteinuria between January 2015 and May 2017. RESULTS: The incidence of FSGS among all dogs biopsied for proteinuria was 26%. Significantly more females (48; 62.3%) than males (29; 37.7%) were affected (P = .04). At the time of biopsy, median serum creatinine concentration (SCr) was 1.2 mg/dL (range, 0.3-8.7), median serum albumin concentration (Alb) was 2.8 g/dL (range, 1.1-4.6), median systolic blood pressure was 153.5 mm Hg (range, 95-260), and median urine protein : creatinine ratio was 5.9 (range, 1.4-22). Median survival time after biopsy was 258 days (range, 26-1003) for dogs that died from all causes (n = 32). Factors that were associated with a shorter survival time included SCr ≥ 2.1 mg/dL (P < .01) and Alb < 2 g/dL (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Most dogs with FSGS were female, and although commonly hypertensive, azotemia, severe hypoalbuminemia and ascites or edema were observed infrequently. Variables significantly associated with survival time were SCr and Alb.