Factors associated with thrombotic disease in dogs with renal proteinuria: A retrospective of 150 cases.

BACKGROUND: Knowledge of additional risk factors for thrombotic disease (TD) among dogs with renal proteinuria is limited; these might differ for TD affecting the systemic arterial (AT), systemic venous (VT), and pulmonary circulation (PT). HYPOTHESIS/OBJECTIVES: To compare signalment and clinicopathological data between dogs with renal proteinuria with or without TD, and between dogs with AT, VT, and PT. ANIMALS: One hundred fifty client-owned dogs with renal proteinuria, 50 of which had TD. METHODS: Retrospective case-controlled study. A database search (2004-2021) identified proteinuric dogs (UPC > 2) with and without TD. Clinicopathological data were obtained from the records. TD and non-TD (NTD) groups were compared by binary logistic regression, and AT, VT, and PT groups by multinomial regression. Normal data presented as mean ± SD, non-normal data presented as median [25th, 75th percentiles]. RESULTS: Cavalier King Charles Spaniels were overrepresented in the TD group (OR = 98.8, 95% CI 2.09-4671, P = .02). Compared to NTD cases, TD cases had higher concentration of neutrophils (11.06 [8.92, 16.58] × 109 /L vs 7.31 [5.63, 11.06] × 109 /L, P = .02), and lower concentration of eosinophils (0 [0, 0.21] × 109 /L vs 0.17 [0.04, 0.41] × 109 /L, P = .002) in blood, and lower serum albumin (2.45 ± 0.73 g/dL vs 2.83 ± 0.73 g/dL, P = .04). AT cases had higher serum albumin concentrations than VT cases (2.73 ± 0.48 g/dL vs 2.17 ± 0.49 g/dL, P = .03) and were older than PT cases (10.6 ± 2.6 years vs 7.0 ± 4.3 years, P = .008). VT cases were older (9.1 ± 4.2 years vs 7.0 ± 4.3 years, P = .008) and had higher serum cholesterol concentration (398 [309-692 mg/dL] vs 255 [155-402 mg/dL], P = .03) than PT cases. CONCLUSIONS AND CLINICAL IMPORTANCE: Differences between thrombus locations could reflect differences in pathogenesis.

Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524.

BACKGROUND: GS-441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS-441524 containing product for the treatment of FIP has not yet been described. OBJECTIVES: Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS-441524 and injectable remdesivir. ANIMALS: Thirty-two client-owned cats diagnosed with effusive or non-effusive FIP including those with ocular and neurological involvement. METHODS: Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow-up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12-week treatment period. RESULTS: Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS-441524 at a median (range) dosage of 15 (10-20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1-5) days. Twenty-six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12-week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment. CONCLUSIONS: We describe the effective use of injectable remdesivir and PO GS-441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement.

Risk factors for upper urinary tract uroliths and ureteral obstruction in cats under referral veterinary care in the United Kingdom.

BACKGROUND: Cats presenting with upper urinary tract uroliths (UUTUs) and ureteral obstruction ("obstructive UUTU") are typically younger than cats with idiopathic CKD that often have incidental nephroliths. HYPOTHESIS: Cats with upper urinary tract urolith have 2 clinical phenotypes; a more aggressive phenotype at risk of obstructive UUTU at a young age and a more benign phenotype in older cats, with reduced risk of obstructive UUTU. OBJECTIVES: Identify risk factors for UUTU and for obstructive UUTU. ANIMALS: Eleven thousand four hundred thirty-one cats were referred for care over 10 years; 521 (4.6%) with UUTU. METHODS: Retrospective VetCompass observational cross-sectional study. Multivariable logistic regression models were performed to identify risk factors for a diagnosis of UUTU vs no UUTU and additionally, obstructive UUTU vs nonobstructive UUTU. RESULTS: Risk factors for UUTU included female sex (odds ratio [OR] 1.6, confidence interval [CI] 1.3-1.9; P < .001), British shorthair, Burmese, Persian, Ragdoll or Tonkinese (vs non-purebred ORs 1.92-3.31; P < .001) breed and being ≥4 years (ORs 2.1-3.9; P < .001). Risk factors for obstructive UUTU were female sex (OR 1.8, CI 1.2-2.6; P = .002), having bilateral uroliths (OR 2.0, CI 1.4-2.9; P = .002) and age, with the odds of obstructive UUTU increasing as age at diagnosis of UUTU decreased (≥12 years, reference category; 8-11.9 years, OR 2.7, CI 1.6-4.5; 4-7.9 years, OR 4.1, CI 2.5-7.0; 0-3.9 years, OR 4.3, CI 2.2-8.6; P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats diagnosed with UUTU at a younger age have a more aggressive phenotype with higher risk of obstructive UUTU compared to cats over 12 years of age diagnosed with UUTU.

Ionized hypercalcemia in 238 cats from a referral hospital population (2009-2019).

BACKGROUND: Ionized calcium concentration ([iCa]) is more sensitive for detecting calcium disturbances than serum total calcium concentration but literature on ionized hypercalcemia in cats is limited. Urolithiasis is a possible adverse consequence of hypercalcemia. HYPOTHESIS/OBJECTIVES: To describe clinical details of diagnoses associated with ionized hypercalcemia in cats and association with urolithiasis. ANIMALS: Cats (238) seen between 2009 and 2019 at a referral hospital with [iCa] above the normal reference interval. METHODS: Observational cross-sectional study. Signalment, serum biochemical and imaging findings were reviewed for cats with ionized hypercalcemia considered to be clinically relevant (>1.41 mmol/L). Data were summarized by cause of hypercalcemia (i.e., diagnosis). RESULTS: Diagnoses for the 238 cats with [iCa] >1.41 mmol/L included: acute kidney injury (AKI; 13%), malignancy-associated (10.1%), idiopathic hypercalcemia (IHC; 10.1%), chronic kidney disease/renal diet-associated (8.4%), iatrogenic (5.5%), primary hyperparathyroidism (2.1%), vitamin D toxicity (2.1%) and granulomatous disease (1.7%). In 112 cases (47.1%), no cause for ionized hypercalcemia could be determined (n = 95), hypercalcemia was transient (n = 12), or the cat was juvenile (<1 year; n = 5). Urolithiasis was identified in 83.3% of AKI, 72.7% of iatrogenic, 61.1% of CKD/renal diet-associated and 50% of IHC cases that were imaged (<50% for other diagnoses). Diagnoses with a high proportion of concurrent total hypercalcemia included primary hyperparathyroidism (100%), vitamin D toxicity (100%), malignancy-associated (71.4%), granulomatous disease (66.7%) and IHC (65.2%). CONCLUSIONS AND CLINICAL IMPORTANCE: Ionized hypercalcemia was most commonly associated with kidney diseases, neoplasia or IHC. The proportion of urolithiasis cases varied by diagnosis.

Treatment failure in hyperthyroid cats after radioiodine (I-131) injection.

BACKGROUND: There is limited published information on the outcome for cats where total thyroxine concentration (TT4) remains elevated after treatment with radioactive iodine (RAI). OBJECTIVE: To determine the frequency of, and predictors for, subsequent treatment failure in cats for which TT4 remains elevated at hospital discharge, and to report clinical outcomes for cats requiring repeat treatment. ANIMALS: One hundred twenty-one cats with TT4 ≥40 nmol/L after treatment with RAI (out of an original, treated study sample of 959 cats). METHODS: Retrospective study. Data regarding signalment, weight, TT4 concentration (before RAI treatment, at discharge, and percentage change), day of sampling, and I-131 dose were acquired. Logistic regression was performed to evaluate predictors of treatment failure. RESULTS: In the 87 cats for which classification was possible, 35 (40%) became euthyroid without further treatment. All TT4 variables and weight normalized RAI dose were independently predictive of subsequent treatment failure. In multivariate analysis, TT4 concentration at discharge (P < .001) and weight normalized RAI dose (P = .04) remained in the final model. All 28 cats with TT4 concentration ≥150 nmol/L at discharge ultimately failed treatment, compared with 13/40 (32.5%) and 11/19 (57.9%) cats with TT4 concentrations of 40-100 nmol/L and 100-150 nmol/L, respectively. Of the 52 cats that failed treatment, 14 were subsequently managed medically, 12 underwent thyroidectomy (4 with carcinoma), 14 had repeat RAI treatment which was successful in 12/14 (86%) cats, and 13 had no further treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with TT4 >150 nmol/L at discharge after RAI might be candidates for immediate repeat treatment.

Changes in retinal vascular diameters in senior and geriatric cats in association with variation in systemic blood pressure.

OBJECTIVES: Early diagnosis of arterial hypertension is essential to prevent target organ damage. In humans, retinal arteriolar narrowing predicts hypertension. This blinded prospective observational study investigated the retinal vessel diameters in senior and geriatric cats of varying systolic blood pressure (SBP) status and evaluated retinal vascular changes in hypertensive cats after treatment. METHODS: Cats with a median age of 14 years (range 9.1-22 years) were categorised into five groups: group 1, healthy normotensive (SBP <140 mmHg; n = 40) cats; group 2, pre-hypertensive (SBP 140-160 mmHg; n = 14) cats; group 3, cats with chronic kidney disease (CKD) and normotensive (n = 26); group 4, cats with CKD and pre-hypertensive (n = 13); and group 5, hypertensive cats (SBP >160 mmHg, n = 15). Colour fundus images (Optibrand ClearView) were assessed for hypertensive lesions. Retinal vascular diameters and bifurcation angles were annotated and calculated using the Vascular Assessment and Measurement Platform for Images of the Retina annotation tool (VAMPIRE-AT). When available, measurements were obtained at 3 and 6 months after amlodipine besylate treatment. RESULTS: Ten hypertensive cats had retinal lesions, most commonly intraretinal haemorrhages and retinal exudates. Arteriole and venule diameters decreased significantly with increasing age (-0.17 ± 0.05 pixels/year [P = 0.0004]; -0.19 ± 0.05 pixels/year). Adjusted means ± SEM for arteriole and venule diameter (pixels) were 6.3 ± 0.2 and 8.9 ± 0.2 (group 1); 7.6 ± 0.3 and 10.1 ± 0.4 (group 2); 6.9 ± 0.2 and 9.5 ± 0.3 (group 3); 7.4 ± 0.3 and 10.0 ± 0.4 (group 4); and 7.0 ± 0.3 and 9.8 ± 0.4 (group 5). Group 1 arteriole and venule diameters were significantly lower than those of groups 2 and 4. Group 2 arteriole bifurcation angle was significantly narrower than those of groups 1 and 3. Post-treatment, vessel diameters decreased significantly at 3 and 6 months in seven hypertensive cats. CONCLUSIONS AND RELEVANCE: Increased age was associated with reduced vascular diameters. Longitudinal studies are required to assess if vessel diameters are a risk indicator for hypertension in cats.

Long-term effect of neutering on plasma luteinising hormone concentration in cats.

OBJECTIVES: The objectives of this study were to validate a commercially available luteinising hormone (LH) cat ELISA, to determine whether the increases in plasma LH concentration that occur after neutering are maintained throughout cats' lives and if other factors such as calendar seasons in both intact and neutered cats, and neutering age in neutered cats, influence plasma LH concentrations. METHODS: Stored plasma samples from client-owned cats were used for the measurement of LH concentrations. Clinical data, including age, sex, age at neutering and medical history, were reviewed. Two populations were included in this study: (1) a senior and geriatric cat population (⩾9 years old), including 18 intact and 18 neutered cats matched for age, sex and month of sample collection; and (2) an adult cat population (2-8 years old), including 45 neutered cats. LH concentrations were measured using a commercially available feline ELISA. RESULTS: Senior and geriatric neutered cats had higher plasma LH concentrations than age-matched intact cats (P <0.001). Calendar season did not influence plasma LH concentrations in the adult (P = 0.727) or senior/geriatric (P = 0.745) cats included in this study. No influence of age at neutering was observed on plasma LH concentrations (P = 0.296). CONCLUSIONS AND RELEVANCE: Neutering causes a significant long-term increase in LH concentrations in cats and further studies are required to determine the consequences on feline health.

The association of bacteriuria with survival and disease progression in cats with azotemic chronic kidney disease.

BACKGROUND: Cats with chronic kidney disease (CKD) have an increased prevalence of positive urine cultures (PUC). Limited information is available regarding the prognosis of cats with CKD and concurrent PUC. OBJECTIVE: To determine the association of PUC with survival time and disease progression in cats with CKD. ANIMALS: Medical records of 509 cats diagnosed with azotemic CKD between 1997 and 2018. METHODS: Cats were classified as having "no-PUC" or "PUC." The PUC cats were further classified as having 1 or multiple PUC, and also were classified based on the presence or absence of clinical signs of urinary tract infection (UTI). Progression of CKD was defined as a plasma creatinine concentration increase of ≥25% within 365 days of CKD diagnosis; PUC also must have occurred within this time frame. Survival time and frequency of CKD progression were compared between groups. RESULTS: No significant difference in survival time was found between cats with no-PUC and cats with any number of PUC (P = .91), or between cats with no-PUC, 1 PUC or multiple PUC (P = .37). Also, no significant difference was found in the frequency of CKD progression between PUC and no-PUC cats (P = .5), or among no-PUC, 1 PUC and multiple PUC cats (P = .22). When assessing cats with clinical signs of lower UTI, no significant difference was found in the frequency of CKD progression between cats with true UTI, subclinical bacteriuria or no-PUC (P = .8). CONCLUSIONS AND CLINICAL IMPORTANCE: When treated with antibiotics, PUC in cats with CKD do not affect disease progression or survival time.

Changes in thyroid and renal function after bilateral thyroidectomy in cats.

BACKGROUND: Iatrogenic hypothyroidism might worsen the prognosis of cats with azotemic CKD after thyroidectomy. Varying thyroxine concentrations influence utility of creatinine in assessing renal function. Symmetric dimethylarginine (SDMA) has limited studies in cats with changing thyroid status. OBJECTIVES: Thyroid status is stable 6 months post-thyroidectomy. Symmetric dimethylarginine and creatinine are linearly associated without influence from total thyroxine concentration (tT4). ANIMALS: Electronic records of 2 first opinion practices were searched using the term "thyroidectomy" to include 81 client-owned cats that had undergone bilateral thyroidectomy. METHODS: Retrospective cross-sectional study assessing thyroid hormone concentrations of 68 cats within 6 months of surgery. A longitudinal study of thyroid status in 23 cats with >18 months follow-up post-thyroidectomy. A generalized estimating equation assessed the associations of bodyweight, tT4 and creatinine concentrations on SDMA concentration. RESULTS: Sixty-eight cats had follow-up within 6 months. Fifteen cats (22%) had persistent, or recurrent, hyperthyroidism and 33 cats (49%) were hypothyroid. Twenty-three of the euthyroid/hypothyroid cats had long-term follow-up (595-1955 days); 4 cats (17%) remained hypothyroid, 19 cats (83%) were euthyroid (often transiently), and 9 of 23 cats (44%) developed recurrent hyperthyroidism. Symmetric dimethylarginine and creatinine were linearly associated, but hyperthyroid cats had higher SDMA concentrations, relative to creatinine (P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats have changes in thyroid function for years after bilateral thyroidectomy, with a high incidence of recurrent hyperthyroidism. Both SDMA and creatinine are affected by thyroxine concentrations, and the effect is greater in hyperthyroid cats.

Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs.

BACKGROUND: Early detection of decreased glomerular filtration rate (GFR) in dogs is challenging. Current methods are insensitive and new biomarkers are required. OBJECTIVE: To compare overall diagnostic performance of serum symmetric dimethylarginine (SDMA) and serum cystatin C to serum creatinine, for detection of decreased GFR in clinically stable dogs, with or without chronic kidney disease (CKD). ANIMALS: Ninety-seven client-owned dogs: 67 dogs with a diagnosis or suspicion of CKD and 30 healthy dogs were prospectively included. METHODS: Prospective diagnostic accuracy study. All dogs underwent physical examination, systemic arterial blood pressure measurement, urinalysis, hematology and blood biochemistry analysis, cardiac and urinary ultrasound examinations, and scintigraphy for estimation of glomerular filtration rate (mGFR). Frozen serum was used for batch analysis of SDMA and cystatin C. RESULTS: The area under the curve of creatinine, SDMA, and cystatin C for detection of an mGFR <30.8 mL/min/L was 0.98 (95% confidence interval [CI], 0.93-1.0), 0.96 (95% CI, 0.91-0.99), and 0.87 (95% CI, 0.79-0.93), respectively. The sensitivity of both creatinine and SDMA at their prespecified cutoffs (115 µmol/L [1.3 mg/dL] and 14 µg/dL) for detection of an abnormal mGFR was 90%. The specificity was 90% for creatinine and 87% for SDMA. When adjusting the cutoff for cystatin C to correspond to a diagnostic sensitivity of 90% (0.49 mg/L), specificity was lower (72%) than that of creatinine and SDMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall diagnostic performance of creatinine and SDMA for detection of decreased mGFR was similar. Overall diagnostic performance of cystatin C was inferior to both creatinine and SDMA.

Development of an estimated glomerular filtration rate formula in cats.

BACKGROUND: Estimated glomerular filtration rate (eGFR) formulas are routinely used in human patients to provide a more accurate evaluation of GFR compared to serum creatinine concentration alone. Similar formulas do not exist for cats. OBJECTIVES: To validate a prediction formula for eGFR in cats based on adjusting serum creatinine concentration. ANIMALS: Client-owned cats with various levels of renal function. METHODS: The study was cross-sectional. Glomerular filtration rate was determined by iohexol clearance. Variables including signalment, biochemical markers, and noninvasive measurements considered to represent surrogate markers of muscle mass were evaluated with the reciprocal of serum creatinine concentration in a multivariable regression model. The derived eGFR formula was subsequently tested in another group of cats and agreement with GFR assessed. RESULTS: The formula was developed in 55 cats. Only a single morphometric measurement (pelvic circumference) along with the reciprocal of serum creatinine concentration (creatinine-1 ) independently predicted GFR in the final multivariate model. The derived eGFR formula was 0.408 + (243.11 × creatinine-1 [µmol/L]) - (0.014 × pelvic circumference [cm]). When the formula was tested in another 25 cats it was not found to offer any advantage over creatinine-1 alone in its relationship with GFR (eGFR, R2 = 0.44, P < .001 vs reciprocal of creatinine, R2 = 0.45, P < .001). Furthermore, agreement between eGFR and GFR was poor. CONCLUSIONS AND CLINICAL IMPORTANCE: An eGFR formula for cats that adjusted serum creatinine concentration for a marker of muscle mass was developed. The formula did not provide a reliable estimate of GFR, and therefore, its routine use cannot be recommended.

ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats.

An update to the 2007 American College of Veterinary Internal Medicine (ACVIM) consensus statement on the identification, evaluation, and management of systemic hypertension in dogs and cats was presented at the 2017 ACVIM Forum in National Harbor, MD. The updated consensus statement is presented here. The consensus statement aims to provide guidance on appropriate diagnosis and treatment of hypertension in dogs and cats.

A longitudinal study of autoantibodies against cytochrome P450 side-chain cleavage enzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism (Addison's disease).

Autoantibodies directed against the P450 side chain cleavage enzyme (P450scc) have been recently described in dogs affected with hypoadrenocorticism, consistent with an immune-mediated pathogenesis of this endocrinopathy. In human autoimmune Addison's disease, autoantibodies may have a predictive value, being detectable before clinical signs developing, and have been shown to persist for a period of time after diagnosis. Furthermore, an autoantibody positive status post-diagnosis has been associated with successful remission of Addison's disease following B-cell depletion, suggesting active immunopathology in these cases. The current study was designed to investigate changes in serum P450scc autoantibody status over time in dogs diagnosed with spontaneous hypoadrenocorticism. P450scc autoantibodies were measured using a species-specific radioimmunoprecipitation assay in an initial cohort of 213 dogs, indicating a prevalence of 24%. Thirty two of these dogs had repeat samples (n = 80 in total) available for analysis. Five dogs were consistently P450scc autoantibody positive in all samples, for up to 425 days following first sampling. Three dogs were initially autoantibody positive, then became seronegative at later time points. One dog, a 1 year old female entire standard poodle, was initially negative for P450scc autoantibodies, but seroconverted 18 months after diagnosis. The remaining 23 dogs with multiple samples available were consistently P450scc autoantibody negative. Persistence was not associated with sex (p = .673). This study demonstrates persistence of P450scc autoantibodies in a subset of dogs affected with hypoadrenocorticism and seroconversion over one year post-diagnosis. P450scc autoantibody reactivity in human autoimmune Addison's disease has been associated with sex, with females having a higher prevalence, possibly due to P450scc expression in the ovary acting as an additional source of antigenic stimulation. However, there was no sex difference in autoantibody persistence in the dogs affected with hypoadrenocorticism. Autontibody persistence in dogs with hypoadrenocorticism might represent persistent pathology, due to residual antigenic stimulation and autoimmune inflammation in the adrenal gland.

The cat as a naturally occurring model of renal interstitial fibrosis: Characterisation of primary feline proximal tubular epithelial cells and comparative pro-fibrotic effects of TGF-ß1.

Chronic kidney disease (CKD) is common in both geriatric cats and aging humans, and is pathologically characterised by chronic tubulointerstitial inflammation and fibrosis in both species. Cats with CKD may represent a spontaneously occurring, non-rodent animal model of human disease, however little is known of feline renal cell biology. In other species, TGF-ß1 signalling in the proximal tubular epithelium is thought to play a key role in the initiation and progression of renal fibrosis. In this study, we first aimed to isolate and characterise feline proximal tubular epithelial cells (FPTEC), comparing them to human primary renal epithelial cells (HREC) and the human proximal tubular cell line HK-2. Secondly, we aimed to examine and compare the effect of human recombinant TGF-ß1 on cell proliferation, pro-apoptotic signalling and genes associated with epithelial-to-mesenchymal transition (EMT) in feline and human renal epithelial cells. FPTEC were successfully isolated from cadaverous feline renal tissue, and demonstrated a marker protein expression profile identical to that of HREC and HK-2. Exposure to TGF-ß1 (0-10 ng/ml) induced a concentration-dependent loss of epithelial morphology and alterations in gene expression consistent with the occurrence of partial EMT in all cell types. This was associated with transcription of downstream pro-fibrotic mediators, growth arrest in FPTEC and HREC (but not HK-2), and increased apoptotic signalling at high concentrations of TGF- ß1. These effects were inhibited by the ALK5 (TGF-ß1RI) antagonist SB431542 (5 µM), suggesting they are mediated via the ALK5/TGF-ß1RII receptor complex. Taken together, these results suggest that TGF-ß1 may be involved in epithelial cell dedifferentiation, growth arrest and apoptosis in feline CKD as in human disease, and that cats may be a useful, naturally occurring model of human CKD.

Repeated measurements of renal function in evaluating its decline in cats.

OBJECTIVES: The aim of this study was to describe the variability in renal function markers in non-azotaemic and azotaemic cats, and also the rate of change in the markers. METHODS: Plasma creatinine concentration and its reciprocal, glomerular filtration rate (GFR) and urine specific gravity (USG) were studied as markers of renal function in client-owned cats. GFR was determined using a corrected slope-intercept iohexol clearance method. Renal function testing was performed at baseline and a second time point. The within-population variability (coefficient of variation; CV%) was determined at the baseline time point. Within-individual variability (CV%) and rate of change over time were determined from the repeated measurements. RESULTS: Twenty-nine cats were included in the study, of which five had azotaemic chronic kidney disease. The within-individual variability (CV%) in creatinine concentration was lower in azotaemic cats than in non-azotaemic cats (6.81% vs 8.82%), whereas the within-individual variability in GFR was higher in azotaemic cats (28.94% vs 19.98%). The within-population variability was greatest for USG (67.86% in azotaemic cats and 38.00% in non-azotaemic cats). There was a negative rate of change in creatinine concentration in azotaemic and non-azotaemic cats (-0.0265 and -0.0344 µmol/l/day, respectively) and a positive rate of change of GFR in azotaemic and non-azotaemic cats (0.0062 and 0.0028 ml/min/day, respectively). CONCLUSIONS AND RELEVANCE: The within-individual variability data suggest creatinine concentration to be the more useful marker for serial monitoring of renal function in azotaemic cats. In contrast, in non-azotaemic cats, GFR is a more useful marker for serial monitoring of renal function. The majority of cats with azotaemic CKD did not have an appreciable decline in renal function during the study.

Investigation of the association between serum protein concentrations and concurrent chronic kidney disease in hyperthyroid cats.

Our objective was to identify if changes in serum protein concentrations occur in hyperthyroidism and to assess their association with the development of azotaemia following treatment. Initially non-azotaemic hyperthyroid cats and healthy older cats were included. Serum concentrations of protein fractions were determined by agarose gel electrophoresis and compared between; hyperthyroid and control cats, initially non-azotaemic hyperthyroid cats which developed azotaemia in a 4month follow up period (masked-azotaemic) and those which remained non-azotaemic, and hyperthyroid cats before and at the time of restoration of euthyroidism. Data are presented as median [25th, 75th percentiles]. Hyperthyroid cats (n=56) had higher serum α2 globulin concentrations (12.5 [10.9, 13.1] g/L vs. 9.8 [3.0, 11.4] g/L; P<0.001) and lower serum γ globulin concentrations (11.4 [9.1, 13.3] g/L vs. 14.0 [12.4, 16.8] g/L; P=0.001) than control cats (n=26). Following treatment, serum total globulin concentration increased (from 38.6 [35.4, 42.8] g/L to 42.3 [39.0, 45.7] g/L; P<0.001), serum α2 globulin concentration decreased (from 12.5 [10.9, 13.9] g/L to 11.5 [10.1, 12.6] g/L; P<0.001) and serum γ globulin concentration increased (from 11.4 [9.0, 13.3] g/L to 14.0 [12.4, 16.8] g/L; P<0.001). Serum concentrations of total globulin or globulin fractions were not significantly different between masked-azotaemic and non azotaemic groups. In conclusion, hyperthyroidism is associated with altered serum concentrations of the α2 and γ globulin fractions, however these changes were not associated with the development of azotaemic chronic kidney disease following treatment.

Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).

Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3ß hydroxysteroid dehydrogenase; 3ßHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3ßHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.

Analysis of DLA-DQB1 and polymorphisms in CTLA4 in Cocker spaniels affected with immune-mediated haemolytic anaemia.

BACKGROUND: Cocker spaniels are predisposed to immune-mediated haemolytic anaemia (IMHA), suggesting that genetic factors influence disease susceptibility. Dog leukocyte antigen (DLA) class II genes encode major histocompatibility complex (MHC) molecules that are involved in antigen presentation to CD4(+) T cells. Several DLA haplotypes have been associated with autoimmune disease, including IMHA, in dogs, and breed specific differences have been identified. Cytotoxic T lymphocyte antigen 4 (CTLA4) is a critical molecule involved in the regulation of T-cell responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 promoter have been shown to be associated with several autoimmune diseases in humans and more recently with diabetes mellitus and hypoadrenocorticism in dogs. The aim of the present study was to investigate whether DLA-DQB1 alleles or CTLA4 promoter variability are associated with risk of IMHA in Cocker spaniels. RESULTS: There were a restricted number of DLA-DQB1 alleles identified, with a high prevalence of DLA-DQB1*007:01 in both groups. A high prevalence of DLA-DQB1 homozygosity was identified, although there was no significant difference between IMHA cases and controls. CTLA4 promoter haplotype diversity was limited in Cocker spaniels, with all dogs expressing at least one copy of haplotype 8. There was no significant difference comparing haplotypes in the IMHA affected group versus control group (p = 0.23). Homozygosity for haplotype 8 was common in Cocker spaniels with IMHA (27/29; 93 %) and in controls (52/63; 83 %), with no statistically significant difference in prevalence between the two groups (p = 0.22). CONCLUSIONS: DLA-DQB1 allele and CTLA4 promoter haplotype were not found to be significantly associated with IMHA in Cocker spaniels. Homozygosity for DLA-DQB1*007:01 and the presence of CTLA4 haplotype 8 in Cocker spaniels might increase overall susceptibility to IMHA in this breed, with other genetic and environmental factors involved in disease expression and progression.

Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury.

Chronic kidney disease (CKD) is a common medical condition of ageing cats. In most cases the underlying aetiology is unknown, but the most frequently reported pathological diagnosis is renal tubulointerstitial fibrosis. Renal fibrosis, characterised by extensive accumulation of extra-cellular matrix within the interstitium, is thought to be the final common pathway for all kidney diseases and is the pathological lesion best correlated with function in both humans and cats. As a convergent pathway, renal fibrosis provides an ideal target for the treatment of CKD and knowledge of the underlying fibrotic process is essential for the future development of novel therapies. There are many mediators and mechanisms of renal fibrosis reported in the literature, of which only a few have been investigated in the cat. This article reviews the process of renal fibrosis and discusses the most commonly cited mediators and mechanisms of progressive renal injury, with particular focus on the potential significance to feline CKD.

Feline double pigtail ureteric stents for management of ureteric obstruction: short- and long-term follow-up of 26 cats.

The objective of this study was to determine the outcome of cats with ureteric obstruction managed with double pigtail ureteric stents and to document the incidence of lower urinary tract signs at long-term follow-up. Data were obtained retrospectively from the medical records (2009-2012) of 26 cats that underwent ureteric stent placement. Owners were contacted for follow-up, and a quality of life questionnaire completed. Survival to discharge after stent placement was 85% (22/26). Prevalence of postoperative uroabdomen necessitating further surgery was 15% (4/26). Stents were replaced 4-28 months after the initial surgery in four cats because of migration, fracture, encrustation causing luminal obstruction or sterile cystitis, respectively. Nine cats were alive at follow-up, which was 3-28 months after the original surgery. Nine cats had azotaemic chronic kidney disease and nine had signs related to sterile cystitis; three of these cats were euthanased as a result of the severity of the signs. Preoperative serum creatinine of the survivors (9.4 mg/dl, n = 9) was not significantly different from that of the non-survivors (6.5 mg/dl, n = 13; P = 0.295). Quality of life was assigned a mean score of 8/10. Median survival of cats following discharge was 419 days (range 44-994 days). Signs consistent with sterile cystitis affected 35% of cats. It was concluded that ureteric stent placement in cats was associated with a 15% mortality rate before hospital discharge. Long-term management of ureteric stents is associated with a high rate of lower urinary tract signs.