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.

Erythrocyte pyruvate kinase deficiency in three West Highland white terriers in Ireland and the UK.

Erythrocyte pyruvate kinase (PK) deficiency is described for the first time in three apparently unrelated West Highland white terriers (WHWT) from Ireland and the UK. All three dogs were diagnosed with markedly regenerative but persistent anaemia and had been treated for presumed immune-mediated haemolytic anaemia (IMHA) before hereditary erythrocyte PK-deficiency was confirmed by breed-specific DNA mutation analysis. This hereditary erythroenzymopathy causes haemolytic anaemia and affects several canine breeds with varying degrees of severity. Although eventually causing osteosclerosis, haemosiderosis and death, PK-deficient dogs can adapt to their anaemia for many years.PK-deficiency should be considered in anaemic WHWTs worldwide particularly in dogs with haemolytic anaemia where evidence for an immune-mediated, infectious or toxic underlying cause is lacking.

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.

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.

Assessment of urinary N-acetyl-beta-D-glucosaminidase activity in geriatric cats with variable plasma creatinine concentrations with and without azotemia.

OBJECTIVE: To validate a non-automated technique for the measurement of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in cats and assess the correlation between NAG index, plasma creatinine concentration, and proteinuria. ANIMALS: 197 client-owned cats (> or = 9 years old; 119 neutered males and 78 neutered females) of which 103 had previously been determined to have chronic kidney disease (CKD). PROCEDURES: Preliminary assay validation was performed for a non-automated colorimetric technique for quantification of NAG activity. The effect of storage of samples was examined. A cross-sectional study was performed to assess urinary NAG index in cats with variable plasma creatinine concentrations and with proteinuria, as quantified by use of the urine protein-to-creatinine ratio (UP:C). RESULTS: Interassay coefficients of variance (CVs) in cats with low (mean, 0.64 U/L), medium (mean, 4.38.U/L), and high (mean, 8.48 U/L) urine NAG activity were 25.9%, 14.4%, and 25.1%, respectively, but intra-assay CVs were < 20%. Urine NAG activity was stable for 4 freeze-thaw cycles and for storage at -20 degrees C. There was no significant difference in log NAG index when cats (n = 197) were grouped according to plasma creatinine concentration, but a moderate positive correlation was found between log NAG index and log UP:C (r2 = 0.259). CONCLUSIONS AND CLINICAL RELEVANCE: N-acetyl-beta-D-glucosaminidase activity can be quantified in feline urine by use of a non-automated colorimetric technique. However, data should be interpreted cautiously because of high interassay CVs. The NAG index in cats with CKD may be indicative of ongoing lysosomal activity rather than active proximal tubular cell damage.

Measurement of urinary cauxin in geriatric cats with variable plasma creatinine concentrations and proteinuria and evaluation of urine cauxin-to-creatinine concentration ratio as a predictor of developing azotemia.

OBJECTIVE: To evaluate urine cauxin immunoreactivity in geriatric cats with variable plasma creatinine concentrations and proteinuria and to assess urinary cauxin-to-creatinine concentration ratio (UC/C) as a predictor of developing azotemia. ANIMALS: 188 client-owned geriatric (>or= 9 years of age) cats. PROCEDURES: A direct immunoassay was developed and validated for the quantification of urinary cauxin relative to a standard curve generated from a urine sample with high cauxin immunoreactivity. Relationships among UC/C, plasma creatinine concentration, and proteinuria were assessed. Nonazotemic cats were recruited and followed for 12 months. Urinary cauxin-to-creatinine concentration ratio was evaluated as a predictor of development of azotemia in these cats. RESULTS: No relationship was evident between UC/C and plasma creatinine concentration. A weak positive correlation was identified between UC/C and urine protein-to-creatinine concentration ratio (r = 0.212). At entry to the longitudinal study, those cats that later developed azotemia had a UC/C that was significantly higher than in those remaining nonazotemic after 12 months. CONCLUSIONS AND CLINICAL RELEVANCE: The UC/C did not vary with severity of azotemia but appeared contributory to the feline urinary proteome. High UC/C values were predictive of the geriatric cats in our study developing azotemia. However, it seems unlikely that UC/C will provide additional information about the measurement of urine protein-to-creatinine concentration ratio as a biomarker for the development of azotemia in cats.

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.

Urinary cortisol/cortisone ratios in hypertensive and normotensive cats.

Hypertension is a common problem in older cats, particularly associated with chronic kidney disease (CKD). Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 predisposes to hypertension in human patients by allowing excessive stimulation of the mineralocorticoid receptor by cortisol. This study was designed to test the hypothesis that reduced conversion of cortisol to cortisone contributes to the development of systemic hypertension in some cats with CKD and idiopathic hypertension (iHT). The study included 60 client-owned cats: 21 clinically normal, 16 normotensive cats with CKD (NTCKD), 14 hypertensive cats with CKD (HTCKD) and nine iHTs. Urine cortisol and cortisone were extracted into dichloromethane and chloroform, respectively, prior to analysis by radioimmunoassay. Data are reported as median and range. The Kruskall-Wallis test was used to compare cortisol:cortisone ratios between groups with post-hoc testing using the Mann-Whitney U test. Wilcoxon signed-ranks test was used to compare results before and after treatment of hypertensive cats with amlodipine. The urinary cortisol:cortisone ratio was significantly higher in clinically normal cats (0.87; 0.46-1.39) when compared to NTCKD (0.60; 0.35-1.20; P<0.001), HTCKD (0.62; 0.34-1.00; P=0.002) and cats with iHT (0.65; 0.46-0.85; P=0.015). No statistical difference was detected between NTCKD, HTCKD and iHT groups. No effect of anti-hypertensive treatment on the urinary cortisol-cortisone ratio was detected (P=0.327). Reduced urinary cortisol to cortisone conversion does not appear to be associated with systemic hypertension in cats. In fact, the cortisol to cortisone shuttle appears to be more effective in cats with CKD (hypertensive and normotensive) and iHT than clinically normal cats. The mechanism for this potentially adaptive response to kidney disease is not clear.

Urinary iodide concentration in hyperthyroid cats.

OBJECTIVE: To compare concentrations of urinary iodide (UI) in euthyroid and untreated hyperthyroid cats. ANIMALS: 118 euthyroid and 88 hyperthyroid client-owned cats from 2 nonreferral veterinary practices. PROCEDURES: Iodide concentration was measured in 5 urine samples collected every 3 to 12 months from selected cats, and variability of results between euthyroid cats and hyperthyroid cats prior to the diagnosis of hyperthyroidism was evaluated via 1-way ANOVA, after logarithmic transformation of UI concentrations (logUIs). The UI concentration in hyperthyroid cats was measured at diagnosis and 2 to 6 weeks and 3 to 6 months after treatment for hyperthyroidism. The pretreatment logUI in hyperthyroid cats was compared with that in euthyroid cats, taking into account the effects of renal function on UI concentration. Iodine intake was estimated in euthyroid cats following calculation of the volume of daily urine output, with a fixed value for iodine concentration in feces. RESULTS: The variability of UI concentrations did not differ significantly between hyperthyroid (n = 10) and euthyroid (8) cats. The logUI increased 2 to 6 weeks after initiation of treatment in hyperthyroid cats (n = 80) and was lower in azotemic versus nonazotemic cats. Hyperthyroid cats had a lower logUI than euthyroid cats, and there was no evidence of deficient iodine intake in euthyroid cats. CONCLUSIONS AND CLINICAL RELEVANCE: The logUI was lower in cats with azotemia and with untreated hyperthyroidism, compared with that in euthyroid cats from the same population. Additional studies are needed to determine whether iodine intake plays a role in the development of hyperthyroidism in cats.

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.

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.

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.

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.

Effect of control of systolic blood pressure on survival in cats with systemic hypertension.

BACKGROUND: Systemic hypertension is a common clinical problem, often occurring in association with renal disease in cats. Limited information is available to assess the effect of blood pressure and the treatment of hypertension on survival. HYPOTHESIS: That adequacy of blood pressure control is associated with the duration of survival in cats with systolic hypertension. ANIMALS: One hundred and forty-one client-owned cats with systolic hypertension. METHODS: Hypertensive cats were treated with amlodipine besylate and were followed until death or the study end point. Time-averaged systolic blood pressure (SBPOT) after implementation of antihypertensive medication and stabilization of systolic blood pressure (SBP) was calculated by using the equation (area under the curve/survival [days]). Cats were divided into quartiles based on their SBPOT, representing varying levels of blood pressure control (median [25th, 75th percentile]: Q1 = 137 [132, 141] mm Hg, Q2 = 148 [145, 151] mm Hg, Q3 = 157 [155, 158] mm Hg, Q4 = 170 [164, 175] mm Hg). Survival and clinical variables were compared between the quartiles. Cox proportional hazard regression analysis was used to determine the association of age, renal function, proteinuria, SBPOT, and the presence of hyperthyroidism on survival. Urine protein to creatinine ratio (UP:C) was compared at diagnosis of hypertension and after initiating treatment. RESULTS: Only UP:C and SBP at diagnosis differed significantly between SBPOT quartiles. Proteinuria was the only variable significantly related to survival in hypertensive cats. A significant decline in UP:C was found in cats treated with amlodipine besylate. CONCLUSIONS AND CLINICAL IMPORTANCE: Proteinuria before and after treatment of hypertension is strongly associated with survival in cats with systolic hypertension. Treatment with amlodipine besylate can result in a significant reduction in UP: C.

Cardiovascular and renal manifestations of hyperthyroidism.

In the simplest terms, hyperthyroidism is the clinical syndrome that results from an excess of thyroid hormones. This review considers the effects of hyperthyroidism on the cardiovascular and renal systems by reviewing the available literature on the clinical manifestations of this syndrome in the cat and also considering experimental studies and experience in other species, including human beings.

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.