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BACKGROUND: Measurement of serum creatinine (sCr) and urea nitrogen fail to detect decreased renal function in many hyperthyroid cats because of low muscle mass and glomerular hyperfiltration of affected cats. Serum symmetric dimethylarginine (sSDMA) is an earlier and more sensitive renal biomarker than sCr. OBJECTIVE: Evaluate sSDMA as a biomarker of renal function in hyperthyroid cats before (T0) and 1 month after (T1) radioiodine (¹³¹I) treatment. ANIMALS: Forty‐seven client‐owned hyperthyroid nonazotemic cats were evaluated at T0 and T1. METHODS: A prospective study in which sCr and sSDMA concentrations were determined in 47 hyperthyroid cats at T0 and at T1. Glomerular filtration rate (GFR) was estimated at T0 and T1 in 10 of these 47 cats using plasma exogenous creatinine clearance test. RESULTS: Serum SDMA was elevated (>14 μg/dL) in 6 of 47 cats at T0 and normalized after treatment in 4 of those cats. All cats remained nonazotemic after treatment. In 10 cats in which GFR was measured, correlation between GFR and sSDMA was low and not significant (τb = −0.35, P = .17 at T0 and τb = −.22, P = .41 at T1), whereas correlation between GFR and sCr was moderate and significant (τb = −0.52, P

Background Serum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. Objectives To evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). Animals Ninety cats were included: 49 CKD and 41 healthy cats. Methods Serum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT

Objectives The objectives of this study were (1) to assess the potential effect of body weight (BW), age, and gender on the most commonly used echocardiographic and conventional Doppler variables in a large population of healthy Cavalier King Charles Spaniels (CKCS), and (2) to establish the corresponding reference intervals (RI). Animals 134 healthy adult CKCS. Methods Ultrasound examinations were performed by trained observers in awake dogs. M-mode variables included left ventricular (LV) end-diastolic and end-systolic diameters, LV free wall and interventricular septal thicknesses at end-diastole and end-systole, and LV fractional shortening (FS%). The left atrium (LA) and aortic (Ao) diameters were measured using a 2D method, and the LA/Ao was calculated. Pulsed-wave Doppler variables included peak systolic aortic and pulmonary flow velocities, mitral E and A waves, and E/A ratio. Effects of BW, age, and gender on these 15 variables were tested using a general linear model, and RIs were determined by applying the statistical procedures recommended by the Clinical and Laboratory Standards Institute. Results A significant BW effect was observed for all variables, except LA/Ao, FS%, and mitral E/A ratio. A significant but negligible effect of gender and age was also observed for 5/15 and 4/15 of the tested variables, respectively. Only the BW effect on M-mode variables was considered as clinically relevant and the corresponding regression-based RIs were calculated. Conclusions Body weight should be taken into account when interpreting echocardiographic values in CKCS, except for LA/Ao, FS%, and mitral E/A ratio.

The objective of this study was to determine the influence of the observer’s level of experience on within- and between-day variability, and the percentage of successful systolic (SAP) and diastolic arterial blood pressure (DAP) measurements obtained by Doppler ultrasonography (DU) in awake cats. For this purpose, six healthy conscious cats were used and four observers with different levels of training performed 144 SAP and DAP measurements on 4 days using DU. Measurements were recorded five consecutive times, and mean values were used for statistical analysis. Only the two most skilled observers – a PhD student in cardiology and a Dipl ECVIM-CA (cardiology) – had within- and between-day coefficients of variation (CVs) for SAP ⩽16% (13–16%). Conversely, the two less experienced observers – a fifth-year student and an assistant – had high between-day CVs (61% and 73%). For DAP, only the most experienced observer (Dipl ECVIM-CA) succeeded in 100% of the attempts, with within- and between-day CVs of 11% and 4%, respectively. Conversely, DAP could not be measured by the other three observers in 8%, 19% and 56% of attempts (from the highest to the lowest level of experience); therefore, the corresponding CV values could not be calculated. In conclusion, SAP may be assessed using DU in healthy awake cats with good repeatability and reproducibility by a well-trained observer. Measurement of DAP is more difficult than of SAP, and needs a longer training period, which represents one of the limitations of DU in cats.

The objective of this prospective observational study was to assess systolic arterial blood pressure (SABP) in small-breed dogs with degenerative mitral valve disease (MVD) from different International Small Animal Cardiac Health Council (ISACHC) heart failure classes. For this purpose, 103 client-owned dogs weighing

Background Increasing salt intake to promote diuresis has been suggested in the management of feline lower urinary tract disease. However, high dietary salt intake might adversely affect blood pressure and renal function. Objectives The objective of this study was to assess the long-term effects of increased salt intake on renal function in healthy aged cats. Methods This study was controlled, randomized, and blinded. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, glomerular filtration rate, blood pressure measurement, cardiac and kidney ultrasonography, and urinary and blood tests were performed before and over 24 months after diet implementation. Statistics were performed using a general linear model. Results Sixteen cats completed the 2 year study. The only variables affected by dietary salt intake were plasma aldosterone and urinary sodium/creatinine ratio, respectively, higher and lower in the control group all over the study period and urinary specific gravity, lower in the high salt diet group at 3 months. Conclusions and Clinical Importance Glomerular filtration rate (GFR), blood pressure, and other routine clinical pathological variables in healthy aged cats were not affected by dietary salt content. The results of this 2 year study do not support the suggestion that chronic increases in dietary salt intake are harmful to renal function in older cats.

Practical relevance: Chronic kidney disease (CKD) is one of the most commonly diagnosed diseases in older cats. In most cats, CKD is also a progressive disease and can be accompanied by a wide range of clinical and clinicopathological changes. These ISFM Consensus Guidelines have been developed by an independent panel of clinicians and academics to provide practical advice on the diagnosis and management of this complex disease. Clinical challenges: Although CKD is a common clinical problem in cats, the manifestations of disease vary between individuals. Thus there is a need for careful and repeat evaluation of cats with CKD and adjustment of therapy according to individual needs. In addition to addressing problems arising from CKD and improving quality of life (QoL) for the patient, therapy may also target slowing the underlying progression of disease and hence prolonging life. While maintaining QoL is of paramount importance in our patients, this can be challenging when multiple therapies are indicated. In some cases it is necessary to prioritise therapy, given an understanding of what is likely to most benefit the individual patient. Evidence base: In preparing these Guidelines, the Panel has carefully reviewed the existing published literature, and has also graded the quality of evidence for different interventions to help to provide practical recommendations on the therapeutic options for feline CKD. This is a field of veterinary medicine that has benefited from some excellent published clinical research and further research findings will undoubtedly modify the recommendations contained in these Guidelines in the future.

The use of transthoracic echocardiography in dolphins has been limited so far owing to technical and anatomical specificities. Anatomic M-mode (AMM) is a postprocessing echocardiographic technique generating M-mode studies from two-dimensional (2D) cineloops independently of the ultrasound beam orientation. The aim of the present study was to determine the within-day (repeatability) and between-day (reproducibility) variability of AMM echocardiography in awake healthy bottlenose dolphins (BN, Tursiops truncatus). Four adult BN trained to lie in left recumbency at the water surface were involved in the protocol. A total of 96 echocardiographic examinations were performed on 4 different days by a trained observer examining each BN 6 times per day. Video clips of 2D left parasternal long-axis views showing the left ventricle (LV) ventrally and the aortic root dorsally were recorded at each examination and analyzed for AMM measurements in a random order. A general linear model was used to determine the within-day and between-day coefficients of variation (CV). All examinations were interpretable allowing calculation of 10 AMM variables (i.e., end-diastolic and end-systolic ventral and dorsal LV myocardial wall thicknesses as well as LV and aortic diameters, mean aortic diameter, and LV shortening fraction). Most within- and between-day CV values (18/20) were

Background: Reference intervals (RI) are pivotal in clinical pathology. The influence of breed on RI has been poorly documented in cats. Hypothesis/Objectives: RI for plasma biochemistry variables are breed-dependent in cats. Animals: Five hundred and thirty-six clinically healthy, fasted, client-owned cats from 4 breeds: Holly Birman (n = 132), Chartreux (n = 129), Maine Coon (n = 139), and Persian (n = 136). Methods: Prospective observational study: Blood samples were collected from the cephalic vein into capillary tubes containing lithium heparin. Plasma glucose, urea, creatinine, total proteins, albumin, calcium, phosphate, sodium, potassium, chloride, and total CO2 concentrations and the activities of alanine aminotransferase and alkaline phosphatase were assayed with a dry slide biochemical analyzer. RI were defined as central 95% intervals bounded by the 2.5th and 97.5th percentiles. Data were analyzed by a linear mixed effects model with type I error rate of 0.05. Results: A significant (P < .05) breed effect was observed for 9/13 variables. The magnitude of the differences between breeds could be clinically relevant for creatinine, glucose, and total protein. Age, body weight, sex, and housing conditions had significant (P < .05) breed-related effects on different variables. Conclusions and Clinical Importance: Breed-specific RI should be considered for cats.

Our aim was (1) to determine the within-day and between-day variability of several indices of systolic and diastolic right ventricular (RV) function by using conventional echocardiography and speckle-tracking echocardiography (STE) (Study 1), (2) to quantify these variables in a large healthy canine population (n = 104) with Doppler-derived estimated systolic pulmonary arterial pressure (SPAP) and left ventricular (LV) function, and (3) to establish the corresponding reference intervals (Study 2). For both studies, RV variables included tricuspid annular plane systolic excursion (TAPSE), right fractional area change (RFAC), STE longitudinal systolic strain (StS) of the RV free wall (RVFW) and of the entire RV (i.e., global RV StS), STE longitudinal systolic RVFW strain rate (SRS), and the diastolic early:late strain rate ratio. All but one within- and between-day coefficients of variation (13/14) were < 15%, the lowest being observed for TAPSE (3.6–9.8%), global RV StS (3.8–9.9%), and RVFW StS (3.7–7.3%). SPAP was weakly and negatively correlated with the TAPSE:body weight ratio (rs = −0.26, p = 0.01) and RVFW SRS (rs = −0.23, p < 0.05). Reference intervals (lower and upper limits with 90% confidence intervals) were provided for all variables. STE provides a non-invasive evaluation of RV function that may be used for clinical investigations in canine cardiology.

Although mitral valve disease (MVD) is the most common canine heart disease, readily available prognostic markers of the disease are still lacking. The aim of this study was to evaluate the comparative ability of N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) and various echocardiographic variables to predict outcome in dogs with MVD.Seventy-four dogs with ISACHC classes 2 and 3 MVD (Groups A and B, respectively) were prospectively recruited. NT-proBNP and several echo-Doppler variables at inclusion were compared as predictors of outcome at 6 months in 54/74 dogs.NT-proBNP was significantly higher in Group B than in Group A (P0.0001), and was the only tested variable significantly different between survivor and non-survivor dogs in both groups (P0.05). In the whole canine population, a threshold of 1500 pmol/L could discriminate survivor from non-survivor dogs with a sensitivity and specificity of 80% and 73%, respectively. When combining ISACHC class with NT-proBNP levels, a cut-off of 1265 pmol/L was predictive of survival in Group A, whereas the cut-off was 2700 pmol/L for Group B.NT-proBNP is correlated with MVD severity and could be used in combination with clinical status to predict cardiac outcome.

Background: The clinical outcome of dogs affected by degenerative mitral valve disease (MVD) without overt clinical signs is still poorly defined, and criteria for identification of animals that are at a higher risk of early decompensation have not yet been determined. Hypothesis: N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) is correlated with mitral regurgitation (MR) severity and can predict disease progression in dogs with asymptomatic MVD. Animals: Seventy-two dogs with asymptomatic MVD, with or without heart enlargement (International Small Animal Cardiac Health Council: ISACHC classes 1a and 1b), and a control group of 22 dogs were prospectively recruited. Methods: Severity of MR was quantitatively assessed from the regurgitation fraction (RF) by the proximal isovelocity surface area method. Consequences of MR were evaluated from measurements of the left atrium/aorta ratio (LA/Ao), fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes indexed to body surface area (EDVI and ESVI). The relevance of these echo-Doppler indices and NT-proBNP for prediction of outcome at 12 months was studied. Results: A significant correlation was found between NT-proBNP and RF, LA/Ao, FS, and EDVI (P < .05). NT-proBNP was higher in dogs with MVD (ISACHC classes 1a and 1b) compared with the control group (P= .025 and < .001, respectively). The difference was not significant when only dogs from ISACHC class 1a with RF < 30% were considered. Lastly, NT-proBNP was higher in dogs that underwent MVD decompensation at 12 months (P < .05). Conclusions and Clinical Importance: NT-proBNP is correlated with MVD severity and prognosis in dogs with asymptomatic MVD.

Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking. Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism. Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis. Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation. Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 (P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 (P < .01). Conclusion: GFR was

The fractional excretion (FE) of a constituent by the kidney is the fraction of the amount filtered by the glomerulus, which is excreted into urine. It is mostly determined for electrolytes, and is expressed as the ratio of the clearance of a given electrolyte to creatinine clearance. The main physiologic factors affecting FE variation are species, age, and the alimentary supply of electrolytes. The value of FE tests in the diagnosis of kidney disease is limited, except in canine Fanconi's syndrome. FEs of many constituents often are increased in chronic kidney disease, but their diagnostic value is no greater than that of plasma creatinine concentration. FEs also are altered in nonrenal diseases such as diabetes mellitus and rhabdomyolysis, and during treatment with xylazine, rehydration fluids, and diuretics. FEs, especially of calcium, phosphates, and magnesium, are useful in clinical nutrition to assess mineral balance. FE is difficult to measure, so its use should be limited to nutritional investigations and nephrology research.

Using paediatric devices to collect venous blood from a cephalic vein in cats offers numerous practical advantages over traditional jugular venepuncture and vacuum closed systems: minimal restraint is required; there is minimal risk of serious injury to the cat; the discomfort associated with venepuncture is reduced by the use of small diameter (25 gauge) needles; very small volumes (200 μl) of blood are extracted; and the risk of vein collapse or haematoma is low. The aim of this study was to compare the haematological and plasma chemistry results obtained from six healthy cats using the two sampling techniques. Five plasma biochemical analytes were measured and a complete haematological examination was performed on each specimen. No clinically relevant difference between the two blood sampling techniques was observed for any variable, indicating that paediatric devices provide a useful alternative to vacuum tubes for venous blood collection in the cat.

Little information is available about the prevalence of renal dysfunction in dogs with chronic valvular heart disease (CVD).Azotemia and a decrease in glomerular filtration rate (GFR) are more severe with increased severity of CVD.124 (study No. 1) and 24 (study No. 2) client-owned dogs with CVD.A retrospective study (study No. 1) was performed to assess the prevalence of azotemia in the New York Heart Association (NYHA) classes of heart failure in dogs with CVD. A prospective study (study No. 2) was then designed to determine GFR in dogs with different degrees of CVD severity. Complete physical examination, electrocardiography, blood pressure measurement, thoracic radiographs, echocardiography, and plasma and urine analyses were also performed.In study No. 1, 50% of the dogs were azotemic and the percentage of azotemic dogs increased with functional class (up to 70% in NYHA class IV patients). In study No. 2, 8/24 dogs were azotemic. Plasma urea and creatinine were higher in NYHA class III-IV dogs compared with class I-II dogs. The GFR was lower (P.001) in NYHA class III-IV dogs (1.7 +/- 0.7 mL/min/kg) than in class I to II dogs (3.1 +/- 0.8 mL/min/kg). Only 1 dog in class I-II had a GFR below 2 mL/min/kg and only 2/9 class III-IV dogs had a GFR above 2 mL/min/kg.Azotemia and renal impairment increase with the severity of congestive heart failure and are frequent findings in dogs with CVD. It remains to be shown if deterioration of renal function is a direct result of progression of the heart disease.

Background: Important characteristics determining the usefulness of a method for glomerular filtration rate (GFR) measurement are convenience, availability, and reproducibility. Hypothesis: The use of different plasma clearance methods could lead to different results and differences in reproducibility. Animals: Twelve healthy cats: 6 young adult cats (age 7-12 months), and 6 aged cats (age 9-12 years) were included in this study. Methods: A cross-over design was used to compare the plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), endo-iohexol (PenICT), and chromium-51 ethylenediaminetetraacetic acid (Cr-51-EDTA), and to investigate reproducibility of these methods. Cats of different ages were included to determine if differences in GFR in young adult versus aged cats would be detected with these methods. The PECCT, PexICT, and PenICT were performed in a combined manner. Plasma data were subjected to noncompartmental (creatinine, exo-iohexol, and endo-iohexol) or bicompartmental ((51)CrEDTA) analysis with a statistical moment approach. Area under the concentration-time curve was calculated using the trapezoidal rule with extrapolation to infinity. Statistical analyses were carried out using a random effects model. Results: Globally, the 4 methods differed significantly (P

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3±0.66 ml/min/kg) was significantly higher ( P

International audience; PURPOSE: The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events. MATERIALS AND METHODS: Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA. RESULTS: 153 genes were found under- or over-expressed at least once among the investigated time-conditions. The eight most discriminant genes were also identified: Two genes (GTP-binding protein RAD and Ankyrin repeat domain protein) were over-expressed at 6 h and six genes between 2 and 21 days (Osteonectin, Fibronectin, Matrix metalloproteinase-2, Collagen alpha 1(I) chain, Collagen alpha 2(I) chain, and Thymosin beta-4). Necrosis, inflammation and regeneration were observed through both the dynamics of gene expression profiles and through the microscopic examinations. CONCLUSION: Our data demonstrate that several pathways are involved in post-injection muscle injury, and that necrosis, inflammation and regeneration are not sequential but occur in parallel.

Limited information is available on pre-analytical variations in plasma analytes in cats. The objectives of this study were to assess the effects of the time of sampling and a standard meal on plasma analytes in healthy cats. Eight healthy, adult, fasted cats underwent blood sampling every 2 h from 8 am to 8 pm twice at a 12 day interval. On the days of sampling, four cats were kept fasted and the others were fed just after the first sample, in a crossover design. Plasma glucose, urea, creatinine, sodium, potassium, chloride, CO2, calcium, phosphate, proteins, albumin, cholesterol and triglycerides, alanine aminotransferase and alkaline phosphatase were assayed on each sample. Effects of time of sampling and meal on plasma biochemistry results were tested using a general linear model. Diurnal variations in tested plasma analytes in fasted cats were negligible except for urea and creatinine, which gave noticeably higher plasma concentrations in the afternoon than in the morning. Observed postprandial variations were of some importance for phosphate and creatinine and of indisputable clinical relevance for CO2 and urea.

International audience; Serum cystatin C (sCysC) is a possible marker for early detection of chronic kidney disease (CKD) in cats. In contrast with serum creatinine (sCr), feline sCysC is not affected by age, breed or sex. However, further biological and clinical validation is required. The objectives of this study were: (1) to investigate if food intake and circadian rhythm affect feline sCysC; (2) to determine the stability of sCysC under different storage conditions, and (3) to investigate if plasma concentrations of CysC (pCysC) differed from sCysC. A crossover study with 10 healthy laboratory cats fed the same commercial dry food was performed to study the influence of feeding and diurnal variation. Storage effects and comparison of pCysC with sCysC were determined using healthy cats (n = 3 and n = 10, respectively) and cats with CKD (n =4 and n = 17, respectively). A significant daily sCysC variation was seen. Pre- and postprandial sCysC and sCr concentrations did not change significantly. Serum CysC significantly increased during storage at room temperature. After freezing, sCysC significantly decreased after 5 and 12 months at both -20 degrees C and -72 degrees C. Plasma CysC was significantly lower than sCysC. These findings suggest that it is not mandatory to fast cats before evaluation of sCysC and sCr. Samples were stable during routinely used storage conditions. Based on these findings, freezing for more than 5 months is not recommended, although additional studies are required to evaluate the clinical relevance of decreased sCysC after prolonged storage. Plasma and serum CysC cannot be compared directly.

Objectives Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. Methods Data from a nine-sample combined plasma exogenous creatinine–iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). Results For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5–98.2%; specificity 60–91.3%) or borderline (sensitivity 91.1–96%; specificity 76.5–81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. Conclusions and relevance These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

Evaluation of skeletal muscle tolerance during development of new drug formulations for i.m. use is most often based on terminal methods performed in the target species after slaughtering. The objective of this study was to evaluate the effect of muscle damage on the pharmacokinetic parameters of the drug delivered into the muscle using an alternative, noninvasive method. Phenylbutazone (PBZ) was used as the test article. Six ewes received increasing volumes of a 20% PBZ i.m. formulation, according to a cross-over design, and an i.v. bolus of the same formulation. Serial blood samples were taken, and a pharmacokinetic analysis of the plasma activity of creatine kinase and plasma PBZ concentrations was carried out. The amount of muscle damage after i.m. administration of 2, 4, or 8 mL of PBZ, calculated from the area under the curve of plasma creatine kinase across time was 36, 76, and 178 g for a 70-kg ewe. The corresponding absolute bioavailability of PBZ was 100 +/- 32%, 96 +/- 19%, and 100 +/- 17%, and the maximal PBZ concentrations were 42 +/- 3.4, 74 +/- 8.8, and 119 +/- 18.2 microg/mL. The plasma clearance of PBZ (i.v.) was 4.2 +/- 0.94 mL.kg(-1).h(-1). In conclusion, the absolute bioavailability of PBZ after i.m. administration was not altered by the increased volume of formulation administered despite the overall increase in the extent of muscle damage.

Daily urinary collection and assessment of glomerular filtration rate (GFR) and effective renal plasma flow were performed in ten 2-month-old Beagle puppies and ten 6-9 year-old Beagle dogs to identify age-associated differences in renal function. The most striking differences in puppies compared to mature dogs were a higher daily urinary volume (+65%), GFR (+87%), free water reabsorption (+159%), a lower daily protein excretion (-88%), and fractional excretion of phosphorus (-35%). Renal function in Beagle puppies, but not mature dogs, was also quite different compared to data published in younger adult dogs.

The objective of this study was to determine the intra- and inter-observer variability of echocardiographic measurements in dogs. Four observers with different levels of experience in echocardiography performed 192 echocardiographic examinations of six dogs on four different days. The lowest within- and between-day coefficients of variation (CV) (%) were 13.8 and 5.2 for the right ventricle in diastole, 8.9 and 4.5 for the interventricular septal thickness in diastole (6.3 and 7.0 in systole), 7.7 and 9.4 for the left ventricular free-wall thickness in diastole (8.1 and 5.2 in systole), 3.1 and 5.0 for the left ventricular end-diastolic diameter (6.2 and 7.0 for end-systolic diameter), 10.2 and 10.8 for the left ventricular shortening fraction, and 8.2 and 9.8 for the left atrium/aorta ratio, respectively. Most of these lowest CVs were observed by the two most experienced observers. Conversely, all maximum values were obtained with the two less experienced observers. These differences in observer-dependent variability may considerably influence the minimum number of animals required to detect a treatment-associated change in echocardiographic variables.

Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P.001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P.05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.

Objectives Diabetic kidney disease (DKD) is a frequent and serious complication in human diabetic patients, but data are limited in cats. This study was undertaken to assess whether diabetic cats are susceptible to DKD. Methods Kidney function was compared between 36 cats with diabetes mellitus (DM), 10 cats with chronic kidney disease (CKD) and 10 age-matched healthy cats by measuring routine kidney variables (serum creatinine [sCreat], serum urea [sUrea], urine specific gravity [USG], urinary protein:creatinine ratio [UPC]), urinary cystatin C:creatinine ratio and glomerular filtration rate (GFR). Urinary cystatin C (uCysC) was measured with a human particle-enhanced nephelometric immunoassay, validated to measure feline cystatin C, in all but two diabetic cats. GFR was evaluated by exo-iohexol clearance in 17 diabetic cats, all cats with CKD and all healthy cats. Results Diabetic cats had significantly (mean ± SD) lower sCreat (123 ± 38 vs 243 ± 80 µmol/l), sUrea (11 ± 3 vs 18 ± 7 mmol/l) and urinary cystatin C:creatinine ratio (6 ± 31 vs 173 ± 242 mg/mol), and a significantly higher USG (1.033 ± 0.012 vs 1.018 ± 0.006) and GFR (2.0 ± 0.7 vs 0.8 ± 0.3 ml/min/kg) compared with cats with CKD. Compared with healthy cats, diabetic cats only had significantly lower USG (1.033 ± 0.012 vs 1.046 ± 0.008). Proteinuria (UPC >0.4) was present in 39% of diabetic cats, in 30% of cats with CKD and in none of the healthy cats. However, the UPC did not differ statistically between the three groups. Conclusions and relevance Based on evaluation of routine kidney variables, GFR and uCysC as a tubular marker at a single time point, a major impact of feline DM on kidney function could not be demonstrated.

Background Plasma variables may be affected by breed or body weight (BW). Small-sized dogs are very common, but no specific reference intervals (RI) are used. Objectives The primary objective of this prospective study was to assess the potential effect of breed, BW, age, and sex on routine plasma analytes and packed cell volume (PCV) in small-sized dogs. A secondary objective was to establish RI in this small-sized population. Methods Blood was sampled under standardized conditions from healthy dogs. PCV and 15 routine plasma variables were measured at the same laboratory. Effects of breed, BW, age, and sex were tested using a general linear model. The procedure recommended by the Clinical and Laboratory Standards Institute was used to establish RI. Results In this study, 154 healthy dogs from 7 breeds were prospectively included. Although a significant effect of breed, BW, sex, or age was evidenced for most variables (except plasma sodium, phosphates, and triglycerides), it was considered as clinically irrelevant. More strikingly, the percentage of values in the reference sample group under the lower limit of the laboratory's RI ranged from 3.8% to 76.6% for 9 variables, and those higher than the upper limit of the laboratory's RI ranged from 4.5% to 9.7% for 7 variables. For example, the RI for creatinine in small-sized dogs was 45–90 μmol/L (vs 54–144 μmol/L for the general dog population). Conclusion Specific RI should be considered for PCV and selected plasma variables in small-sized dogs.

International audience; High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some elderly people, salt-sensitive patients and animal models.

International audience; Glomerular filtration rate (GFR) is considered to be the best indicator of overall kidney function. The major objectives of this study were to compare plasma exogenous creatinine clearance (PECC) with a reference method, to establish reference intervals (RIs) for PECC and to assess the effects of indexation of GFR to bodyweight (BW) in cats. PECC was compared with urinary clearance of exogenous creatinine (UECC) in six clinically healthy domestic shorthair cats (experiment 1). Tentative RIs were determined according to current guidelines and the effects of indexation to BW and of covariables on GFR were assessed in 43 clinically healthy cats of various breeds (experiment 2). PECC was 15% higher than UECC (P

Objectives—To investigate and validate noninvasive methods for the quantitative evaluation of postinjection muscle damage. Animals—5 adult sheep. Procedures—Muscle lesions were induced twice in the lumbar region of the longissimus dorsi muscles (2 sides) by IM administration of a 20% formulation of long-acting oxytetracycline (20 mg/kg of body weight). Clinical signs and local cutaneous temperature above the injection site were recorded. Muscle lesions were quantitatively evaluated by ultrasonography and by use of pharmacokinetic analysis of plasma creatine kinase activity, and both were compared with a comprehensive planimetric computer-assisted analysis of the injection sites after euthanasia. Results—Transient cutaneous hypothermia (temperature change, –3.9 ± 0.62 C) and subsequent persistent hyperthermia (3.1 ± 1.35 C) were observed after the administrations. Despite coefficient of variation < 10% for precision of ultrasonographic measurement of normal muscle, measurements of the lesions, with coefficient of variation > 60% for precision, were systematically underestimated. Quantitative evaluation of muscle damage by use of pharmacokinetic analysis of creatine kinase (12.1 ± 4.96 g) was in agreement with results of macroscopic planimetric evaluation (10.8 ± 3.64 g). Conclusions and Clinical Relevance—Ultrasonography cannot be used for quantitative assessment of postinjection muscle damage. Pharmacokinetic analysis of creatine kinase provides an accurate quantitative evaluation of macroscopic muscle damage after IM administration of drugs. (Am J Vet Res 2001;62:1698–1705)

Although gastrointestinal complications are common in patients with renal disease, the effects of renal dysfunction on bowel motility and gut transit times are not well known. We assessed gastrointestinal electromyographic activity, gastric emptying rate, orocolonic transit time, oroanal transit time, and xylose absorption before and after surgically inducing a 66% decrease in glomerular filtration rate in dogs. Moderate renal failure induced no gross or microscopic gastrointestinal lesions but caused a 16–42% increase in gastrointestinal motility indexes. We found a 24% decrease in the propagation velocity of the myoelectrical migrating complex in the duodenojejunal segment, a 30% decrease in phase I duration in duodenal and jejunal regions, a 20% increase in the total irregular electrical activity of the small intestine, and a 22% increase in duration of the meal response in the duodenum and jejunum. Renal failure did not change xylose absorption, gastric emptying rate, and orocolonic transit time but decreased colonic transit time by 38%. The mean weight of feces was increased. These results indicate that moderate renal failure alters duodenojejunal motility and decreases colonic transit time.

Background. Gene delivery of biologically active molecules to the kidney may have potential therapeutic applications in renal and cardiovascular diseases. Recombinant adenovirus is one of the most efficient vectors for in vivo gene delivery. However, in vivo toxicity at the site of administration has to be evaluated for the successful use of adenovirus-mediated gene transfer. The aim of this study was to document precisely the short-term safety of different routes of intra-renal adenoviral administration and to compare their transduction efficiency. Methods. Dog puppies were injected with an adenoviral vector expressing the β-galactosidase reporter gene in both kidneys via three different routes, i.e. intra-renal-ureteral route (IU) and intra-renal-arterial route with (IAC) or without (IA) clamping of the renal vein. Toxicity of viral administration was assayed on day 4 at both physiological and histological levels. Renal samples were monitored for the presence of nuclear β-galactosidase-expressing cells. Results. All renal physiological parameters (glomerular filtration rate, effective renal plasma flow, and electrolyte excretion fractions) remained stable whatever the route of viral administration. No histological lesion was detected in any of the haematoxylin-eosinstained kidney sections, and there was no evidence of ischaemia-reperfusion injury in the kidneys subjected to venous clamping. Efficient transgene expression was obtained in dog kidneys following IAC and IU injection of adenoviral vectors. Gene transfer via the IAC route induced gene expression predominantly in the cortical interstitial cells. Retrograde IU adenoviral injection resulted in reduced transduction efficiency compared with the IAC route, with transgene expression occurring mainly in the distal tubular and pyelic epithelial cells. Conclusions. The two major findings of this study were (i) the absence of acute histological and functional renal alteration following intra-arterial and intra-ureteral injections of adenoviral vectors in both kidneys of healthy dogs, and (ii) the efficiency of transgene expression with specific cellular targeting according to the route of administration.

The specificity of a diagnostic test for a given disease, i.e. the percentage of true negatives, can be calculated from either the results from a group of healthy animals or possibly from a group which also contains diseased animals which are free of the particular disease for which the test has been performed. The specificity may be much lower in the latter case and the predictive value of positives thus greatly reduced. In the example of creatine kinase being used for the diagnosis of muscle diseases in dogs, the specificity at the thresholds of 105 and 150 U/L (upper limits of the 95% and 99.7% interquantiles) decreased from 0.98 and 1.0 to 0.66 and 0.78, respectively.

The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right nephrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 +/- 9.8 versus 14.9 +/- 5.0 micrograms.minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 +/- 26.4 to 31.9 +/- 17.7 ng/mL) (P .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment.

We describe a chronic model of lymphatico-venous bypass in pigs with emphasis to surgical considerations, major per- and postoperative complications. A catheter (silicone or heparin coated polyurethane) was inserted in the thoracic duct of nine pigs via a right intercostal thoracotomy. A second catheter was surgically inserted in the jugular vein and the bypass was secured on the back of the animals. Pigs were monitored for capnography, end-tidal carbon dioxide, systolic, diastolic and mean blood pressure, heart rate, and rectal temperature. Apnea was recorded in every pig in the recovery period leading to one death. During the postoperative period, ventricular tachycardia in 2/9 pigs and hypothermia in 5/9 pigs were recorded. Bypass was effective in 5/9 pigs. Clotting occurred only with silicone catheters (1/2) but not with heparin-coated catheters. In the heparin-coated catheters group, bypass was patent up to 15 days with no major complication recorded. Sampling of lymph was allowed from 2 to 15 days. The immediate postoperative period is critical and should be carefully monitored. Although complications were present, the surgical technique was efficient. Chronic catheterization of thoracic duct is useful in biomedical research in the fields of intensive care, gastro-enterology, pharmacokinetic and hematology studies.

Muscle damage in dogs anaesthetised with halothane and propofol was quantified by measurement of the area under the curve of plasma creatine kinase (CK) versus time. Plasma CK remained unchanged during anaesthesia for two and a half and five hours. Following halothane anaesthesia of dogs (resting on one side directly on the surgical table or on cushions, and with or without rotation of the body every 30 minutes), plasma CK was elevated in some animals to 10,000 U/litre by the 12th hour (baseline value < or = 100 u/litre), whereas it remained almost unchanged in other animals. Plasma CK then returned to reference values on day 2 or 3. The mean equivalent of muscle damaged ranged from 0.6 to 0.9 g/kg bodyweight. No muscle damage could be demonstrated in animals anaesthetised with propofol. It is therefore concluded that plasma CK should not be used as a diagnostic aid following halothane anaesthesia because of false positives due to the halothane anaesthesia itself and that propofol is best suited for the investigation of muscle damage due to surgical procedures.

The pharmacokinetic disposition of tolfenamic acid, an NSAID, after a single administration of tolfenamic acid (4 mg kg(-1)) by the intravenous (IV) route was compared in eight dogs before and after a surgically induced renal failure. Renal impairment was confirmed by a significant increase (p 0.05) and the mean residence time was significantly decreased from 606 +/- 199 to 373 +/- 302 min (p or = 99%) was observed. These results suggest that renal insufficiency could increase hepatic metabolism and/or alter the enterohepatic cycle of TA.

International audience; Plasma NT-proBNP has previously been evaluated in dogs with degenerative mitral valve disease (DMVD). However, reference intervals (RI) established according to the Clinical Laboratory and Standards Institute (CLSI) recommendations have never been provided. The objectives of this prospective study were to assess effects of breed, body weight, age, and sex on plasma NT-proBNP, and to establish RI according to CLSI for this biomarker in a large population of dogs predisposed to DMVD. 183 Healthy small-sized dogs from 7 breeds were included. Assays were performed by ELISA. Effects of covariates were tested using a general linear model. Although a sex effect was demonstrated (P=0.01), no significant effect of breed, body weight or age was shown. The proposed RI was 157-2842 pmol/L. 7% of dogs had plasma NT-proBNP >2617 pmol/L, and were considered as outliers despite normal cardiovascular examination. In conclusion, plasma NT-proBNP may be high in a few healthy small-sized dogs.

Background Spironolactone treatment in humans is associated with an increased risk of hyperkalemia and renal dysfunction. Hypothesis Dogs with cardiac disease treated with spironolactone, in addition to conventional therapy, are not at higher risk for adverse events (AEs) than those receiving solely conventional therapy. Animals One hundred and ninety-six client-owned dogs with naturally occurring myxomatous mitral valve disease. Methods Prospective, double-blinded field study with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin-converting enzyme inhibitor, plus furosemide and digoxin if needed). Safety was compared between treatment groups, using the frequency of AEs, death caused by cardiac disease, renal disease, or both, and variations in serum sodium, potassium, urea, and creatinine concentrations. For the latter, population-specific reference intervals were established and out of range values (ORV) analyzed. Results The number of AEs was similar in the spironolactone and reference groups (188 and 208, respectively), when followed for median duration of 217 days (range [2–1,333]). At each study time point, the percentage of dogs showing ORV was similar between groups. There were a higher number of deaths because of cardiac disease, renal disease or both in the reference group (30.7% versus 13.7%) (P = .0043). Conclusions and Clinical Importance Dogs with heart failure receiving spironolactone in addition to conventional treatment are not at a higher risk for AEs, death caused by cardiac disease, renal disease, or both, hyperkalemia, or azotemia.

The main objective of this study was to assess glomerular filtration rate (GFR) in the camels (Camelus dromedarius) under free water access and dehydration conditions (after a 34 days-period of water deprivation) using plasma exogenous creatinine clearance without urine collection. Trials were carried out on six nonpregnant, non-lactating and healthy female camels. Creatinine was administered as an IV bolus at a dose of 16 mg/kg body weight. Blood samples were collected at predetermined times over 24 h post-injection. Plasma creatinine concentration was analysed using Jaffé method. Creatinine clearance was calculated by pharmacokinetic analysis using a non-compartmental approach. Water deprivation induced a significant 15%- decrease in body weight but did not affect haematocrit and total plasma proteins. Mean corpuscular volume increased and red blood cells number decreased in dehydrated conditions. Dehydration produced a significant 30%-increase in plasma creatinine and mean residence time and a significant 20%-decrease in GFR. In conclusion, water deprivation decreased glomerular filtration and plasma exogenous creatinine clearance test could be used as a practical method for GFR assessment in dromedary camel in field conditions.

Summary Intramuscular injections of a vitamin B preparation, imidocarb,imidocarb+lidocaine, and a preparation of salts of fatty acids produced significant increases in plasma creatine kinase activity in groups of five to six dogs. Activities peaked between 3 and 8 h, and were as high as 23 times base values with the fatty acid salts preparation. Quantification of the equivalent muscle damage gave means of 0.04, 0.25, 0.23 and 0.30 g kg −1 body weight, respectively, for each of the above preparations.

Quantitative evaluation of organ damage can be achieved by non-invasive, direct or indirect methods. Direct methods include echography, tomography, scintigraphy and magnetic resonance. The accuracy of these imaging techniques has been demonstrated in human medicine. Most of them have not been validated in animals, however, and their use is limited by cost. Indirect methods are based on determination of the total release of intracellular markers (mainly enzymes) into body fluids. Quantification of organ damage depends on extracellular disposition of the marker. Thus, in the kidney, the marker is directly and totally leaked into the urine and is voided at each micturition. The amount of marker eliminated in this way allows easy quantification of organ damage occurring during the period preceding the micturition. Muscle markers with molecular weights exceeding 50 kDa reach the blood via the lymph. This results in (a) partial inactivation, (b) delay between cell damage and increased plasma concentration and (c) accumulation in the plasma as long as delivery into the plasma exceeds clearance. In such cases, quantitative evaluation requires pharmacokinetic tools and calculation of the area under the curve (concentration vs time) and of the plasma clearance. Comparison of the intensity and chronology of markers located in different cell compartments may contribute to the understanding of pathophysiological events.

Background Azotemia occurs frequently in dogs with degenerative mitral valve disease (DMVD). It could indicate changes in renal hemodynamics. Hypothesis/Objectives To assess the renal resistive index (RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo-Doppler parameters, several plasma variables, and RI. Animals Fifty-five dogs with naturally occurring DVMD were used (ISACHC class 1 [n = 28], 2 [n = 19], and 3 [n = 8]). Methods Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo-Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N-terminal pro-B-type natriuretic peptide concentrations (NT-proBNP) were determined. Statistical links between variables and RI were tested by means of a general linear model. Results Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased (P

Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs >= 10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.

International audience; Renal function was assessed in 25 dogs with Cushing's syndrome and in 12 healthy controls. Routine renal parameters and glomerular filtration rate (GFR) were measured and urinary biomarkers such as urinary albumin (uALB), urinary immunoglobulin G (uIgG), and urinary retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-beta-D-glucosaminidase activity (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma exo- (Cl-exo) and endo-iohexol (Cl-endo) clearance were used to measure GFR. Based on a Mann-Whitney U test, urea and Clexo did not differ, sCr was significantly lower, and UPC, uALB/c, uIgG/c, uRBP/c, uNAG/c and Cl-endo were higher in the dogs with Cushing's syndrome when compared with controls. The findings indicate that glomerular and tubular function are both altered in dogs with Cushing's syndrome. Further longitudinal studies will be required to elucidate the pathogenesis of the changes in GFR. (C) 2011 Elsevier Ltd. All rights reserved.