Bayesian evaluation of sensitivity and specificity of blood culture media and hypoglycemia in sepsis-suspected calves.

BACKGROUND: Sepsis is a life-threatening condition for which critically important antimicrobials are often indicated. The value of blood culture for sepsis is indisputable, but appropriate guidelines on sampling and interpretation are currently lacking in cattle. OBJECTIVE: Compare the diagnostic accuracy of 2 blood culture media (pediatric plus [PP] and plus aerobic [PA]) and hypoglycemia for bacteremia detection. Estimate the contamination risk of blood cultures in critically ill calves. ANIMALS: One hundred twenty-six critically ill calves, 0 to 114 days. METHODS: Retrospective cross-sectional study in which the performance of PP, PA and hypoglycemia to diagnose sepsis was assessed using a Bayesian latent class model. A Cox proportional hazards model was used to compare time to positivity (TTP). Potential contamination was descriptively analyzed. Isolates were considered relevant when they were; member of the Enterobacterales, isolated from both blood cultures vials, or well-known, significant bovine pathogens. RESULTS: The sensitivities for PP, PA, and hypoglycemia were higher when excluding assumed contaminants; 68.7% (95% credibility interval = 30.5%-93.7%), 87.5% (47.0%-99.5%), and 61.3% (49.7%-72.4%), respectively. Specificity was estimated at 95.1% (82.2%-99.7%), 94.2% (80.7%-99.7%), and 72.4% (64.6%-79.6%), respectively. Out of 121 interpretable samples, 14.9% grew a presumed contaminant in PA, PP, or both. There was no significant difference in the TTP between PA and PP. CONCLUSIONS AND CLINICAL IMPORTANCE: PA and PP appear to outperform hypoglycemia as diagnostic tests for sepsis. PA seems most sensitive, but a larger sample size is required to verify this. Accuracy increased greatly after excluding assumed contaminants. The type of culture did not influence TTP or the contamination rate.

Serum symmetric dimethylarginine in older dogs: Reference interval and comparison of a gold standard method with the ELISA.

BACKGROUND: Serum symmetric dimethylarginine (SDMA) is used to screen for renal dysfunction in dogs. The gold standard technique for measuring SDMA, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is not widely available. Age-specific reference intervals for SDMA in older dogs are lacking. OBJECTIVES: Prospective study in older dogs to validate a commercially available LC-MS/MS method for SDMA, compare SDMA concentrations with concentrations measured using ELISA and obtain a reference interval (RI) for older dogs using both methods. ANIMALS: Client-owned older dogs undergoing health screening. METHODS: The LC-MS/MS method was analytically validated (limit of detection, precision, and linearity). Serum was sent cooled overnight for ELISA or was frozen at -80°C until batch analysis using LC-MS/MS. Results of LC-MS/MS and ELISA were compared and RIs for older dogs were calculated according to international guidelines. RESULTS: The LC-MS/MS method showed good linearity (r2 = .99) and precision (coefficient of variation <10%), with a laboratory RI between 8.0 and 14.0 µg/dL. Paired measurements were available from 118 different dogs. Median SDMA concentration were 9.4 (range, 5.0-21.2) using LC-MS/MS and 12.0 (range, 5.0-22.0) µg/dL using ELISA. Both methods significantly differed with a mean difference of 2.2 µg/dL. The RI for older dogs for LC-MS/MS was 4.4-15.0 µg/dL, and for ELISA was 6.4-17.4 µg/dL. CONCLUSIONS AND CLINICAL IMPORTANCE: The ELISA provided significantly higher SDMA concentrations compared to the validated LC-MS/MS method, indicating the need for device- or assay-specific RI. The obtained age-specific RI for SDMA is considerably higher in older dogs compared to the general laboratory RI.

Determination of age-specific reference intervals for selected serum and urinary biomarkers in elderly cats.

OBJECTIVES: Annual health screening is recommended in elderly cats to allow the early detection of conditions such as chronic kidney disease (CKD) and hyperthyroidism. Nevertheless, age-specific reference intervals (RIs) for renal and thyroid parameters in this population are lacking. The aim of this study was to determine age-specific RIs for selected serum and urine biomarkers related to CKD and hyperthyroidism, namely serum creatinine (sCr), symmetric dimethylarginine (SDMA), phosphate (P), total calcium (tCa), total thyroxine (TT4), urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). These RIs were established for elderly cats (aged ⩾7 years) in general, as well as for mature adult cats (aged 7-10 years) and senior cats (aged >10 years) separately. METHODS: A prospective study was conducted on client-owned cats aged ⩾7 years and considered healthy by their owners. The cats were screened to rule out metabolic and systemic diseases by means of a thorough history, complete physical examination, blood examination and urinalysis. The data from 206 healthy elderly cats (134 mature adult and 72 senior cats) were included. Age-appropriate RIs were determined following the guidelines of the American Society of Veterinary Clinical Pathology and compared with existing laboratory RIs. RESULTS: Clinically relevant differences between the age-specific RI and the laboratory RI were found for several variables. Compared with the laboratory RI, the upper limit of the RI for cats aged ⩾7 years was lower for sCr, TT4 and P, and higher for SDMA. The lower limit of the age-appropriate RI was lower for USG. The new RI was almost identical to the existing laboratory RI for tCa and UPC. CONCLUSIONS AND RELEVANCE: Using age-specific RIs for renal and thyroid biomarkers in mature adult and senior cats has important clinical consequences for the interpretation of health screening results in elderly cats. This confirms the need to adapt laboratory RIs to the specific animal population for which the RI will be used.

Biological variation of urinary protein: Creatinine ratio and urine specific gravity in cats.

BACKGROUND: Laboratory results are influenced by presence and severity of disease, as well as preanalytical factors, analytical variation, and biological variation. Biological variation data for urinary protein: creatinine ratio (UPC) and urine specific gravity (USG) in cats are lacking. OBJECTIVES: Determine the biological variation of UPC and USG in cats. ANIMALS: Eighty healthy client-owned cats. METHODS: Prospective study. Urine was collected on days 0, 14, and 56 from all 80 cats to investigate the persistence of borderline or overt proteinuria or suboptimal urine concentration. In 15 of these cats, urine was collected weekly from day 0 to 42 to calculate the index of individuality (II) and reference change value (RCV), and on days 56 and 57 to evaluate day-to-day variability of UPC and USG. RESULTS: Borderline or overt proteinuria (UPC ≥0.2) was present in 18/80 (23%) cats at baseline and persisted on 3 occasions in 2 months in 8/18 (44%) cats. Urine concentration was suboptimal at inclusion (USG <1.035) in 8/80 (10%) cats and at all 3 time points during 2 months in 3/8 (38%) cats. The II of UPC and USG indicated intermediate individuality. The 1-sided RCV was 82% for UPC and 36% for USG. Proteinuria substage was identical on 2 consecutive days in 13/15 (87%) cats, and urine concentrating ability remained the same in all 15 cats. CONCLUSIONS AND CLINICAL IMPORTANCE: A >82% increase in UPC in a healthy cat is not solely attributable to physiological and analytical variation. For USG, a decrease of >36% is considered clinically relevant.

Effect of storage temperature and time on measurement of serum symmetric dimethylarginine concentration using point-of-care and commercial laboratory analyzers in cats and dogs.

BACKGROUND: Stability of serum symmetric dimethylarginine (sSDMA) during short- and long-term storage has not been assessed for the immunoassay of the Point-of-Care IDEXX Catalyst DX (POC) analyzer and the Enzyme Multiplied Immunoassay Technique of IDEXX commercial laboratory (CL). Also, the agreement between both analyzers is questioned. OBJECTIVES: To determine (a) the effect of storage time and temperature on sSDMA measured by POC and CL; (b) the agreement between sSDMA measured by POC and CL; and (c) the imprecision of the POC. ANIMALS: Serum of cats (n = 17) and dogs (n = 18) with a range of SDMA concentrations (6 to >100 µg/dL). METHODS: Based on an equivalence trial with predefined equivalence range (-3.0 to +3.0 µg/dL) and using T0 as baseline, stability was evaluated after 24 hours at 22°C and 4°C (POC); after 7 days at 4°C (POC and CL) and after 10 and 24 months at -24°C and -80°C (CL). Bland-Altman plots enabled method comparison. Imprecision of the POC was assessed by duplicate sSDMA measurements at T0. RESULTS: The POC analyzer produced equivalent sSDMA measurements if samples were stored for 24 hours at 4°C (95% confidence interval [CI]: -2.5-2.0 µg/dL), but not when stored for 24 hours at room temperature (RT; 95% CI: -4.1 to 0.5 µg/dL) or after 7 days at 4°C (95% CI: -3.6-1.0 µg/dL). The CL analyzer was less affected by preanalytical variation with clinically similar results obtained when samples were stored for 7 days at 4°C (95% CI: -2.2 to 2.4 µg/dL) and for at least 24 months at -24°C (95% CI: -1.7 to 2.9 µg/dL) and -80°C (95% CI: -1.5 to 3 µg/dL). A relevant mean difference of -2.3 µg/dL between both analyzers was found. Duplicate POC measurements were equivalent (95% CI: -2.6 to 2.0 µg/dL). CONCLUSIONS: Delayed analysis may significantly change sSDMA depending on storage and measurement conditions. Interchangeable use of assays should be done with caution because analytical variation could be interpreted as clinically relevant change.

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.

Reference interval, longitudinal variability and reliability of activated clotting time in healthy dogs using a point-of-care analyser.

BACKGROUND: Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy. OBJECTIVES: To determine a reference interval (RI) for ACT in dogs using a point-of-care analyser, to quantify intra-subject within- and between-day variability, to quantify analyser reliability and inter-analyser agreement and to study the influence of a delay in measurement. METHODS: Forty-two healthy dogs were included. Measurements were performed on fresh venous blood using the i-STAT 1 analyser. The RI was determined using the Robust method. Intra-subject within-day variability and between-day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter-analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6). RESULTS: Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra-subject within- and between-day variability were 8.1% and 10.4%, respectively, resulting in a significant between-day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis. CONCLUSIONS: Our study provides an RI for ACT in healthy dogs using the i-STAT 1 and suggests low intra-subject within- and between-day variability. Analyser reliability and inter-analyser agreement were good; however, analysis delay and between-day differences could significantly influence ACT results.

Dogs with congenital extrahepatic portosystemic shunts that have persistent shunting after surgery have a higher prevalence of urolithiasis.

OBJECTIVE: To report the presence of urolithiasis in dogs long-term after gradual attenuation of congenital extrahepatic portosystemic shunts (cEHPSS). ANIMALS: 25 client-owned dogs that underwent gradual attenuation of a cEHPSS, of which 19 had a closed cEHPSS and 6 developed multiple acquired portosystemic shunts (MAPSS) following surgery. PROCEDURES: A retrospective study with prospective follow-up was performed. Dogs that underwent cEHPSS surgery and had their postoperative cEHPSS status determined by transsplenic portal scintigraphy or CT angiography 3 months postoperatively were prospectively contacted and invited for a long-term follow-up visit (a minimum of 6 months postoperatively). Retrospective data were collected, and during the prospective follow-up visit a thorough history, blood tests and urinalysis, and ultrasonography of the urinary tract were performed to assess the presence of urinary signs and urolithiasis. RESULTS: Of 25 included dogs, 1 of 19 (5%) dogs with closed cEHPSS and 4 of 6 (67%) dogs with MAPSS had urolithiasis at long-term follow-up. Three (50%) dogs with MAPSS developed new uroliths. Long-term, dogs with closed cEHPSS that initially presented with and without urolithiasis had significantly less urolithiasis compared to dogs with MAPSS (P = .013 and P = .010, respectively). In the 4 dogs with closed cEHPSS that initially presented with nephrolithiasis, nephroliths became smaller or were no longer visible at the long-term follow-up visit. CLINICAL RELEVANCE: Dogs that developed MAPSS following cEHPSS surgery are at greater risk of urolithiasis compared to those with closed cEHPSS. Furthermore, ammonium urate uroliths might dissolve if portosystemic shunting ceases to exist.

Effect of laboratory and sample storage factors on urinary protein:creatinine ratios and clinical decision making in cats.

BACKGROUND: Urinary protein:creatinine ratio (UPC) results affect the diagnosis, prognosis, and therapy of chronic kidney disease in cats. OBJECTIVES: To investigate the interlaboratory and intralaboratory variability and the effect of storage on UPC and International Renal Interest Society (IRIS) proteinuria substaging in cats. ANIMALS: Healthy and diseased client-owned cats. METHODS: Prospective study. Urine of 60 cats was randomly sent to 4 (of 9) participating laboratories (to assess interlaboratory variability) and per cat, 2 laboratories each received 2 aliquots (to determine intralaboratory variability). Samples of 23 cats were analyzed in the same laboratory the day of collection, after preservation at 22°C for 1 day and at 4°C during 1-7 days (short-term storage) and at -24°C and -80°C for 6-12 months (long-term storage). Storage conditions were compared by equivalence testing. RESULTS: UPCs showed good interclass correlation (ICC-inter, 0.90) and excellent intraclass correlation (ICC-intra, 0.99). However, in 30/60 (50%) cats at least 1 of 4 laboratories assigned a different IRIS proteinuria substage. Urinary protein:creatinine ratio remained stable with short-term storage, but not after 6 months storage at -24°C and after 12 months storage at -24°C or -80°C. Long-term storage caused a change in IRIS proteinuria substage in 27% of cats, whereas a shift occurred only in 4% of cats during short-term storage. CONCLUSIONS AND CLINICAL IMPORTANCE: Laboratory choice for UPC measurement can result in different IRIS substaging for the same cat, whereas urine storage at room temperature for 1 day or in the refrigerator for up to 7 days does not clinically affect UPC.

Radioiodine treatment in hyperthyroid cats: insights into the characteristics of owners and their cats, and owner motivation and perceptions.

OBJECTIVES: Radioiodine (131I) therapy is the most appropriate treatment option for many hyperthyroid cats, as it is minimally invasive and often curative. Nevertheless, 131I treatment is not always pursued by owners. Hence, it is important to obtain more insight into owner satisfaction during and after 131I treatment, and their decision-making process. In this study, we describe the characteristics of owners and their hyperthyroid cats referred for 131I therapy, and determine owners' motivation and how they experienced the 131I treatment of their cat. METHODS: A survey was sent to owners whose cats underwent 131I therapy (n = 1071) between 2010 and 2017 at Ghent University. The survey contained 35 questions with tick-box or free-text answer options concerning family situation, pet insurance, previous therapy, comorbidities, motivation for 131I therapy and owner perception of this treatment. RESULTS: In total, 438 owners completed 94% or more of the questionnaire. Over half of the cats (55%) had received previous medical, dietary or surgical treatment. Motivations for changing the initial therapy to 131I therapy included difficulties in administering medication (31%), insufficient improvement in clinical signs (23%), side effects (16%) and following the referring veterinarian's advice (16%). Almost a fifth of owners (18%) were not informed about the existence of 131I therapy by their veterinarian and found information on 131I treatment online or through friends. Hospitalising their cat was very distressing for 17% of owners. Most owners (92%) were satisfied with the treatment. Reasons for dissatisfaction were insufficient communication, iatrogenic hypothyroidism, persistent hyperthyroidism and comorbidities post-treatment. CONCLUSIONS AND RELEVANCE: Our study stresses the importance of communication regarding the possible outcome of 131I treatment, the importance of managing underlying comorbidities before treatment and anticipating the stress of owners during their cat's hospitalisation period. The results of this study could help in improving client communication when advising on 131I treatment.

Systolic blood pressure measurements with Doppler ultrasonic flow detector and high-definition oscillometry are comparable on population level but show large intra-individual differences in apparently healthy elderly dogs.

OBJECTIVE: Agreement of systolic blood pressure measurements (SBP) between noninvasive blood pressure devices in conscious dogs is poorly studied. Situational hypertension is expected in clinics, but studies are lacking. This study aimed to compare SBP measurements obtained with Doppler ultrasonic flow detector (Doppler) versus high-definition oscillometry (HDO) in clinics and at home and to estimate the prevalence of situational hypertension in conscious, apparently healthy elderly dogs. ANIMALS: 122 apparently healthy elderly or geriatric dogs were prospectively recruited. PROCEDURES: Systolic blood pressure was obtained consecutively with Doppler and HDO techniques in a randomized order per dog, following a standardized protocol. An at-home measurement was advised for in-clinic hypertensive dogs (SBP ≥ 160 mmHg), also using both devices. RESULTS: Dual measurements were available in 102 dogs. Median SBP was 147.3 mmHg (range, 105 to 239 mmHg) for Doppler and 152.3 mmHg (range, 113 to 221 mmHg) for HDO. Forty-six percent (56/122) were hypertensive, of which 9% (11/122) were hypertensive with both methods. No significant difference was found between the 2 devices in the global study population or within the group of hypertensive dogs. Repeated at-home measurements were performed in 20/56 (35.7%) hypertensive dogs, resulting in a 10 and 26 mmHg lower median SBP value for Doppler and HDO, respectively (P > .05). In-clinic situational hypertension was presumed in 8/20 (40%) dogs. CLINICAL RELEVANCE: The choice of the noninvasive blood pressure device did not significantly impact SBP results, but large interindividual differences in SBP between techniques occurred. Situational hypertension was frequently observed in clinic.

Urinary liver-type fatty acid-binding protein in clinically healthy elderly cats: Evaluation of its potential to detect IRIS stage 1 chronic kidney disease and borderline proteinuria.

BACKGROUND: Urinary liver-type fatty acid-binding protein (uL-FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL-FABP for unknown reasons. OBJECTIVES: The objective of this study was to evaluate uL-FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. METHODS: This was a cross-sectional study. One hundred ninety-six clinically healthy client-owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L-FABP was measured using a validated commercially available feline L-FABP ELISA. RESULTS: Overall, uL-FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL-FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL-FABP concentrations (median 1.79 ng/ml, range 0.79-3.66 ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL-FABP concentration, whereas the other five cats with detectable uL-FABP concentrations were non-proteinuric. CONCLUSION: With the current assay, the screening potential of uL-FABP as an early biomarker for feline CKD is limited as uL-FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria.

The prevalence of the ABCB1-1Δ variant in a clinical veterinary setting: The risk of not genotyping.

Multidrug sensitivity is an autosomal recessive disorder in dogs caused by a 4-bp deletion in the ABCB1 gene, often referred to as the ABCB1-1Δ variant. This disease has a high prevalence in some breeds and causes adverse reactions to certain drugs when given in normal doses. Though most dogs known to be at risk are of the collie lineage or were traced back to it, the variant has also been described in several seemingly unrelated breeds. It is generally advised to genotype dogs at risk before treating them. However, there seems to be a discrepancy between the advice and current veterinary practices, as a recent study in Belgium and the Netherlands showed that most veterinarians never order a DNA test. To assess the possible risk of not testing for multidrug sensitivity in a clinical setting, the ABCB1-1Δ variant allele frequency was established in a sample of 286 dogs from a veterinary clinic. This frequency was compared to the allelic frequency in 599 samples specifically sent for genetic testing. While the allelic frequency in the sample for genetic testing was high (21.6%) and in line with the general reports, the allelic frequency in the clinical setting was low (0.2%), demonstrating an enormous difference between laboratory and clinical frequencies. Because of the low frequency of the disease-causing variant in the general clinical population, the risk of encountering a dog displaying multidrug sensitivity despite not genotyping seems to be low. As the variant was only found in an at-risk breed, the current recommendation of routinely genotyping at-risk breeds before treatment seems justified.

Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats.

BACKGROUND: In people and dogs, torasemide has higher bioavailability, longer half-life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited. OBJECTIVE: To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin-angiotensin-aldosterone system (RAAS). ANIMALS: Six clinically healthy adult European shorthair cats. METHODS: Randomized 4-period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model. RESULTS: Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half-life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose-dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: A single torasemide dose leads to a significant increase in diuresis and renin-angiotensin-aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.

Evaluation of different blood tests in dogs with extrahepatic portosystemic shunts to assess shunt closure after surgical treatment.

OBJECTIVE: To determine the sensitivity and specificity of different individual and combined blood tests to assess extrahepatic portosystemic shunt (EHPSS) closure after gradual attenuation of EHPSS in dogs. STUDY DESIGN: Clinical prospective study. ANIMALS: Twenty client-owned dogs with EHPSS. METHODS: Fasting ammonia (FA), preprandial, postprandial, and paired serum bile acids (SBA), the lidocaine/monoethylglycylxylidide (L/MEGX) test, and serum hyaluronic acid (SHA) were performed at diagnosis, and 1, 3, and 6 months postoperatively. Transsplenic portal scintigraphy was performed to determine EHPSS closure 3 months postoperatively. Their sensitivity and specificity in determining shunt closure postoperatively were calculated. RESULTS: When assessing a single blood parameter, FA had the highest specificity (100%), whereas SHA and MEGX measured 15 min after lidocaine administration (T15) had the highest sensitivity (96.9% and 96.2%, respectively) for determining shunt closure postoperatively. The most promising blood test combinations were SHA (sensitivity 96.9%, specificity 81.8%), combined with the L/MEGX test (MEGX at T15: sensitivity 100%, specificity 72.4%) or the L/MEGX test (MEGX at T15) combined with either FA (sensitivity 100%, specificity 82.8%) or postprandial SBA (sensitivity 100%, specificity 81.5%). CONCLUSION: Both SHA and the L/MEGX test were sensitive tests for determining shunt closure after gradual attenuation of EHPSS. Test performances could even be improved by combining these tests with each other or with traditional tests such as FA or postprandial SBA. CLINICAL SIGNIFICANCE: Although SHA and the L/MEGX test are sensitive blood tests for determining EHPSS closure, especially when combined with traditional blood tests, imaging is still needed to confirm EHPSS closure.

Comparison of diet, lactulose, and metronidazole combinations in the control of pre-surgical clinical signs in dogs with congenital extrahepatic portosystemic shunts.

BACKGROUND: Hepatic supportive diet (HSD), lactulose, and antimicrobials are medical treatments for dogs with congenital extrahepatic portosystemic shunts (cEHPSS). The relative contribution of these treatment components is currently unknown. OBJECTIVES: To determine which treatment combinations are most efficacious in pre-surgical control of clinical signs of cEHPSS in dogs. ANIMALS: Thirty-six dogs with untreated cEHPSS. METHODS: Three-arm randomized clinical trial. At inclusion (T0), dogs were divided into 3 groups: HSD (n = 12), HSD + lactulose (n = 12), or HSD + metronidazole (n = 12) and received the randomized treatment for 4 weeks (T1) followed by combined treatment of HSD + lactulose + metronidazole for 2 weeks or until cEHPSS attenuation (T2). Clinical score as well as fasting ammonia (FA) and C-reactive protein (CRP) concentrations were compared among groups and time points. RESULTS: Thirty-four dogs were evaluated. Thirty-four dogs reached T1 and 29 dogs T2. At T1, clinical scores decreased in the HSD + lactulose (n = 11; P = .001), but not in the HSD (n = 8; P = .96) and HSD + metronidazole (n = 10; P = .06) groups. Adding metronidazole to HSD + lactulose (n = 11) did not result in further clinical score improvement (T2; P = 1.000). Moderate and weak correlation between clinical score and FA and clinical score and CRP was present (ρ = .35, P < .001; ρ = .27, P = .01, respectively) with FA decreasing over time on medical treatment (P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Combined HSD + lactulose seems sufficient for pre-surgical cEHPSS stabilization unlike sole HSD or HSD + metronidazole. Medical treatment of cEHPSS clinical signs decreases FA.

Total lipid concentration of hairs increases after successful attenuation of extrahepatic portosystemic shunts in dogs.

BACKGROUND: Skin and coat quality can reflect nutritional deficiencies in humans and dogs with liver diseases. HYPOTHESIS/OBJECTIVES: Determine skin and coat quality based on a scoring protocol and skin biopsies in dogs with an extrahepatic portosystemic shunt (EHPSS), and determine total lipid concentrations in hairs of dogs at time of surgery and 3 months after successful shunt closure. ANIMALS: Ten client-owned dogs that underwent successful gradual attenuation of EHPSS, as defined by transsplenic portal scintigraphy, were included. MATERIALS AND METHODS: A prospective cohort study was performed. All dogs underwent gradual attenuation of the EHPSS. Skin and coat scoring was performed at diagnosis, surgery, and 1 and 3 months postoperatively. Hair was plucked from the lumbar region for total lipid analysis and an 8 mm punch skin biopsy was taken at time of surgery and 3 months postoperatively, when the dogs underwent transsplenic portal scintigraphy to determine EHPSS closure. RESULTS: No significant differences were observed in skin and coat scoring over time. Total lipid concentrations of hairs increased significantly from surgery to 3 months postoperatively [30 µg/mg hair (13-56 µg/mg hair) to 47 µg/mg hair (25-63 µg/mg hair); p = 0.005]. Skin biopsies showed the presence of significantly more scales 3 months postoperatively (p = 0.018). CONCLUSIONS AND CLINICAL RELEVANCE: A significant increase in total lipid concentrations in hairs suggests that successful surgical attenuation of EHPSS improves either intestinal absorption of lipids, fat metabolism in the liver, or a combination of both.

Contexte - La qualité de la peau et du pelage peut refléter des carences nutritionnelles chez les humains et les chiens atteints de maladies du foie. Hypothèse/Objectifs - Déterminer la qualité de la peau et du pelage sur la base d'un protocole de notation et de biopsies cutanées chez les chiens avec un shunt portosystémique extrahépatique (EHPSS), et déterminer les concentrations totales de lipides dans les poils des chiens au moment de la chirurgie et trois mois après la fermeture réussie du shunt. Animaux - Dix chiens appartenant à des clients qui ont subi une atténuation progressive réussie de l'EHPSS, telle que définie par la scintigraphie portale trans-splénique, ont été inclus. Matériels et méthodes - Une étude de cohorte prospective a été réalisée. Tous les chiens ont subi une atténuation progressive de l'EHPSS. Une notation de la peau et du pelage a été réalisée au moment du diagnostic, de la chirurgie et un et trois mois après l'opération. Les cheveux ont été prélevés dans la région lombaire pour une analyse des lipides totaux et une biopsie cutanée à l'emporte-pièce de 8 mm a été effectuée au moment de la chirurgie et trois mois après l'opération, lorsque les chiens ont subi une scintigraphie portale trans-splénique pour déterminer la fermeture de l'EHPSS. Résultats - Aucune différence significative n'a été observée dans la notation de la peau et du pelage au fil du temps. Les concentrations totales de lipides dans les poils ont augmenté de manière significative entre la chirurgie et trois mois après l'opération [30 µg/mg de poils (13-56 µg/mg de poils) à 47 µg/mg de poils (25-63 µg/mg de poils) ; P = 0,005]. Les biopsies cutanées ont montré la présence de significativement plus d'écailles trois mois après l'opération (P = 0,018). Conclusions et pertinence clinique - Une augmentation significative des concentrations totales de lipides dans les cheveux suggère qu'une atténuation chirurgicale réussie de l'EHPSS améliore soit l'absorption intestinale des lipides, soit le métabolisme des graisses dans le foie, soit une combinaison des deux.

Introducción- la calidad de la piel y el pelaje puede reflejar deficiencias nutricionales en humanos y perros con enfermedades hepáticas. Hipótesis/Objetivos- determinar la calidad de la piel y el pelaje según un protocolo de valoración y en biopsias de piel en perros con shunt portosistémico extrahepática (EHPSS) y determinar las concentraciones totales de lípidos en el pelo de los perros en el momento de la cirugía y tres meses después del tratamiento exitoso del shunt. Animales- se incluyeron diez perros de propietarios particulares que se sometieron a una atenuación gradual exitosa de EHPSS, según se identificó mediante por gammagrafía portal transesplénica. Materiales y métodos - Se realizó un estudio de cohorte prospectivo. A todos los perros se les realizó una atenuación gradual del EHPSS. La valoración de la piel y el pelaje se realizó en el momento del diagnóstico, la cirugía y uno y tres meses después de la operación. Se arrancó el pelo de la región lumbar para el análisis de lípidos totales y se tomó una biopsia de piel con sacabocados (punch) de 8 mm en el momento de la cirugía y tres meses después de la operación, cuando los perros se sometieron a una gammagrafía portal transesplénica para determinar el cierre de EHPSS. Resultados- no se observaron diferencias significativas en la valoración de la piel y el pelaje a lo largo del tiempo. Las concentraciones de lípidos totales del pelo aumentó significativamente desde la cirugía hasta los tres meses posteriores a la operación [30 µg/mg de pelo (13-56 µg/mg de pelo) a 47 µg/mg de cabello (25-63 µg/mg de pelo); P = 0,005]. Las biopsias de piel mostraron la presencia de mayor cantidad de escamas de forma significativa tres meses después de la operación (P = 0,018). Conclusiones y relevancia clínica- un aumento significativo en las concentraciones de lípidos totales en el pelo sugiere que la atenuación quirúrgica exitosa de EHPSS mejora la absorción intestinal de lípidos, el metabolismo de las grasas en el hígado o una combinación de ambos.

Contexto - A qualidade da pele e dos pelos pode refletir deficiências nutricionais em humanos e cães com hepatopatias. Hipótese/Objetivos - Determinar a qualidade da pele e pelos baseada em um protocolo de escore e biópsias cutâneas em cães com shunt portossistêmico extra-hepático (EHPSS) e determinar as concentrações lipídicas totais nos pelos de cães no momento da cirurgia e três meses após o fechamento bem-sucedido do shunt. Animais - Foram incluídos dez cães de proprietários submetidos à atenuação gradual do EHPSS bem-sucedida, confirmada por cintilografia portal transesplênica. Materiais e métodos - Realizou-se um estudo de coorte prospectivo. Todos os cães foram submetidos à atenuação gradual do EHPSS. A classificação de pele e pelos em escores foi realizada no diagnóstico, cirurgia, e com um e três meses de pós-operatório. Os pelos foram arrancados da região lombar para análise lipídica total e uma biópsia com punch de 8mm foi coletada no momento da cirurgia e com três meses de pós-operatório, quando os cães foram submetidos à cintilografia portal transesplênica para determinar o fechamento do EHPSS. Resultados - Não foram observadas diferenças significativas nos escores de pele e pelos ao longo do tempo. As concentrações de lipídicas totais aumentaram significativamente da cirurgia aos três meses de pós-operatório [30 µg/mg de pelo (13-56 µg/mg pelo) para 47 µg/mg de pelo (25-63 µg/mg de pelo); P = 0,005]. As biópsias cutâneas revelaram a presença de significativamente mais escamas com três meses de pós-operatório (P = 0,018). Conclusões e relevância clínica - O aumento significativo de concentrações lipídicas totais nos pelos sugere que a atenuação cirúrgica de EHPSS bem-sucedida melhora tanto a absorção intestinal de lipídeos quanto o metabolismo de gordura no fígado, ou uma combinação dos dois.

Diagnostic value of liver function tests and ultrasonography in dogs with suspected congenital portosystemic shunts.

BACKGROUND: Diagnosing a congenital portosystemic shunt (cPSS) in dogs can be challenging. The current study aims to report diagnostic performance of fasting ammonia (FA), preprandial, postprandial and paired serum bile acids (SBA) and abdominal ultrasound (aUS) in dogs suspected of having a cPSS. METHODS: Medical records of dogs suspected of having a cPSS at initial presentation were retrospectively reviewed. RESULTS: In total, 192 dogs suspected of cPSS were included: a cPSS was confirmed in 147 dogs and excluded in 45 dogs. FA had the best combined sensitivity and specificity (77.4 and 93.3%, respectively) to diagnose cPSS. The sensitivity and negative predictive value were 100.0% for paired SBA, making paired SBA the best test to exclude cPSS in this population. Sensitivity and specificity of aUS were 80.8 and 90.0%, respectively. CONCLUSIONS: In dogs with clinical signs compatible with cPSS, elevated FA is suggestive of cPSS, whereas normal paired SBA makes the presence of a cPSS unlikely. Although aUS is a useful tool to diagnose cPSS, additional imaging is required to visualize cPSS in almost 20% of cases. Furthermore, the localisation of cPSS can be misdiagnosed, especially in case of extrahepatic cPSS that do not insert into the prehepatic vena cava.

Renal biomarkers in cats: A review of the current status in chronic kidney disease.

Serum creatinine concentration, the classical biomarker of chronic kidney disease (CKD) in cats, has important limitations that decrease its value as a biomarker of early CKD. Recently, serum symmetric dimethylarginine concentration was introduced as a novel glomerular filtration rate biomarker for the early detection of CKD in cats. However, data on its specificity are still limited. The limitations of conventional biomarkers and the desire for early therapeutic intervention in cats with CKD to improve outcomes have prompted the discovery and validation of novel renal biomarkers to detect glomerular or tubular dysfunction. Changes in the serum or urinary concentrations of these biomarkers may indicate early kidney damage or predict the progression of kidney before changes in conventional biomarkers are detectable. This review summarizes current knowledge on renal biomarkers in CKD in cats, a field that has progressed substantially over the last 5 years.

Persistent hypercobalaminemia three months after successful gradual attenuation of extrahepatic shunts in dogs: a prospective cohort study.

BACKGROUND: Deficiencies in vitamin A and D and disorders in the vitamin B complex are often present in people with chronic liver diseases. So far, the serum concentrations of these vitamins have not yet been studied in dogs with congenital extrahepatic portosystemic shunts (EHPSS), who also have some degree of liver dysfunction. The objective was to assess serum vitamin concentrations in dogs with EHPSS from diagnosis to complete closure. A prospective cohort study was performed using ten client-owned dogs with EHPSS, closed after gradual surgical attenuation. Serum concentrations of vitamin A, 25-hydroxyvitamin D, folic acid, cobalamin and methylmalonic acid (MMA) were measured at diagnosis prior to institution of medical therapy, prior to surgery, and three months after gradual attenuation and complete closure of the EHPSS. RESULTS: At diagnosis, median serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid were 18.2 µg/dL (8.8 - 79.5 µg/dL), 51.8 ng/mL (19.4 - 109.0 ng/mL), and 8.1 µg/L (5.2 - 14.5 µg/L), respectively, which increased significantly postoperatively (88.3 µg/dL (51.6 - 182.2 µg/dL, P=0.005), 89.6 ng/mL (49.3 - >150.0 ng/mL, P =0.005), and 14.8 µg/L (11.5 - 17.7 µg/L, P <0.001), respectively). Median serum cobalamin concentrations were 735.5 ng/L (470 - 1388 ng/L) at diagnosis and did not significantly decrease postoperatively (P =0.122). Both at diagnosis and three months postoperatively 7/10 dogs had hypercobalaminemia. CONCLUSIONS: Serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid significantly increase after surgical attenuation. Nevertheless, persistent hypercobalaminemia is suggestive of ongoing liver dysfunction, despite successful surgery.