Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

BACKGROUND: High-salt diets promote urine dilution and decrease urolithiasis risk. OBJECTIVE: Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). ANIMALS: Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). METHODS: Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. RESULTS: Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.

Plasma symmetric dimethylarginine and creatinine concentrations and glomerular filtration rate in cats with normal and decreased renal function.

BACKGROUND: Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. OBJECTIVES: To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. ANIMALS: Forty-nine client-owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. METHODS: Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. RESULTS: Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMAplasma (26.7 ± 9.9 µg/dL) and sCr (249.7 ± 71.6 µmol/L [2.8 ± 0.8 mg/dL]; both P < .001) values. SDMAplasma (τB = -0.57; P < .001) and sCr (τB = -0.56; P < .001) were significantly correlated with GFR. SDMAplasma (τB = 0.52; P < .001) had a significant relationship with sCr. SDMAplasma and sCr had similar sensitivity (76%-94% and 71%-88%, respectively) in detecting reduced renal function. Creatinine had higher specificity (94%-96%) than SDMAplasma (75%-76%) (P < .05). CONCLUSION AND CLINICAL IMPORTANCE: In this study of azotemic and nonazotemic cats, SDMA was a reliable marker to identify decreased GFR. However, superiority of SDMA over sCr could not be confirmed.

Assessment of symmetric dimethylarginine as a biomarker of renal function in hyperthyroid cats treated with radioiodine.

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 (131 I) 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 < .05 at T0 and τb = -.53, P = <.05 at T1). CONCLUSIONS AND CLINICAL IMPORTANCE: Careful interpretation of mildly increased sSDMA with normal sCr in hyperthyroid cats is warranted as sSDMA values might normalize after resolution of hyperthyroidism in some cats. In this population of hyperthyroid cats, sSDMA was poorly correlated with GFR.

Quantitative assessment of systolic and diastolic right ventricular function by echocardiography and speckle-tracking imaging: a prospective study in 104 dogs.

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.

Long-term follow-up of renal function assessing serum cystatin C in dogs with diabetes mellitus or hyperadrenocorticism.

BACKGROUND: Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC. OBJECTIVES: The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC. METHODS: A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs. RESULTS: The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group. CONCLUSIONS: A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.

ISFM Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease.

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.

Influence of the observer's level of experience on systolic and diastolic arterial blood pressure measurements using Doppler ultrasonography in healthy conscious cats.

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.

Routine plasma biochemistry analytes in clinically healthy cats: within-day variations and effects of a standard meal.

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.

Routine kidney variables, glomerular filtration rate and urinary cystatin C in cats with diabetes mellitus, cats with chronic kidney disease and healthy cats.

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.

Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate.

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.

Basal plasma concentrations of routine variables and packed cell volume in clinically healthy adult small-sized dogs: effect of breed, body weight, age, and gender, and establishment of reference intervals.

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.

Echocardiography and conventional Doppler examination in clinically healthy adult Cavalier King Charles Spaniels: effect of body weight, age, and gender, and establishment of reference intervals.

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.

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog.

BACKGROUND: Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). RESULTS: Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 µg/L for creeping speed, 284 µg/L for the lameness score, 161 µg/L for the ground reaction vertical force and 193 µg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. CONCLUSIONS: Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was determined for confirmatory clinical trials.

Basal plasma concentrations of N-terminal pro-B-type natriuretic peptide in clinically healthy adult small size dogs: effect of body weight, age, gender and breed, and reference intervals.

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.

Feline CKD: Pathophysiology and risk factors--what do we know?

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is one of the most frequently encountered disorders in cats, having increased in prevalence in recent decades. Although the underlying cause is rarely identified, the common final outcome of feline CKD is tubulointerstitial fibrosis. Knowledge of CKD pathophysiology is necessary for optimal individualised patient management, especially with regard to diagnosis and treatment of extrarenal complications. PATIENT GROUP: CKD is most common in senior and geriatric cats, but should be considered in any feline patient with ureterolithiasis, hyperthyroidism, retrovirus infection, systemic hypertension, cardiovascular disease or urinary tract infection. EVIDENCE BASE: Most of our knowledge of the pathogenesis of CKD is extrapolated from human nephrology and experimental animal studies. There is, therefore, a need for further studies in cats. The prevalence of clinical signs in feline CKD is well documented. Several concurrent diseases associated with CKD have also been reported in cats, especially in the geriatric population, but there is no or only limited published evidence demonstrating a cause-and-effect relationship between most of these conditions and CKD. Studies performed over the past 15 years have nevertheless allowed identification of major risk factors (proteinuria, plasma phosphate and plasma creatinine) influencing the progression of feline CKD. CLINICAL CHALLENGES: Clinical signs occur in the late stages of renal disease, so populations at higher risk of CKD should be screened routinely. CKD-associated complications (systemic hypertension, secondary renal hyperparathyroidism, hypokalaemia, anaemia, metabolic acidosis) must not be overlooked as they may affect the progression of disease. Disease progression is itself unpredictable and renal function may remain stable for extended periods. Most cats with early CKD do not progress to end-stage CKD before they die. AUDIENCE: General practitioners play a major role in screening feline patients at risk of development or progression of CKD.

Within-day and between-day variability of transthoracic anatomic M-mode echocardiography in the awake bottlenose dolphin (Tursiops truncatus).

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 <15%, the lowest being observed for the end-diastolic LV diameter (1.6%). In conclusion, AMM provides a simple non-invasive evaluation of heart morphology and function in the awake BN with good repeatability and reproducibility of the measurements. Further studies are required to determine the corresponding reference intervals.

Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function.

OBJECTIVE: To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. ANIMALS: 50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. PROCEDURES: Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. RESULTS: Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.

Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration.

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.

Comparison of Doppler ultrasonography and high-definition oscillometry for blood pressure measurements in healthy awake dogs.

OBJECTIVE: To determine the intra- and interobserver variability of systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) measurements obtained with 2 indirect methods in awake dogs and percentage of successful measurements. ANIMALS: 6 healthy conscious adult dogs. PROCEDURES: 4 observers with different levels of training measured SAP and DAP on 4 days by use of Doppler ultrasonography (DU) and high-definition oscillometry (HDO). The examinations were randomized. Measurements for each technique were recorded 5 consecutive times, and mean values (total, 720 measurements) were used for statistical analysis. RESULTS: All within- and between-day coefficients of variation (CVs) for SAP were < 15% irrespective of the observer or method (HDO, 3.6% to 14.1%; DU, 4.1% to 12.4%). Conversely, half the CVs for DAP were > 15% with the highest within- and between-day CVs obtained by the least experienced observer by use of DU (19.5% and 25.9%, respectively). All attempts with HDO were successful, whereas DAP could not be measured by use of DU by the least experienced observer in 17% of attempts. CONCLUSIONS AND CLINICAL RELEVANCE: SAP may be assessed in healthy dogs by use of DU and HDO with good repeatability and reproducibility after a short period of training. Conversely, the variability of DAP is higher and longer training is required to assess DAP via DU than via HDO.