Rosanne E. Jepson

Evaluation of predictors of the development of azotemia in cats.

BACKGROUND Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification. HYPOTHESIS Clinical variables, urine concentrating ability, proteinuria, and N-acetyl-beta-D-glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months. ANIMALS Client-owned nonazotemic geriatric (>or=9 years) cats. METHODS Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia. RESULTS One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis (P<or=.05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant. CONCLUSIONS AND CLINICAL IMPORTANCE This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.

A comparison of CAT Doppler and oscillometric Memoprint machines for non-invasive blood pressure measurement in conscious cats

Indirect blood pressure measurements were compared in 28 conscious cats using Doppler and oscillometric blood pressure-measuring devices. Ten cats were used to compare Doppler measurements between two examiners and 18 cats were used to compare Doppler and oscillometric measurements. The Doppler machine obtained systolic and diastolic blood pressure readings in 100% and 51% of attempts, respectively. With the oscillometric machine, systolic and diastolic blood pressure readings were obtained in 52% of the attempts. With the Doppler, measures of mean systolic blood pressure between two examiners were positively correlated, but there was no correlation for diastolic blood pressure measures. When comparing the results obtained by Doppler and oscillometric machines there was no significant difference between mean systolic blood pressure readings, but the oscillometric machine produced significantly higher estimates of diastolic blood pressure. In both cases, the standard deviations for the oscillometric machine were considerably larger than those for the Doppler machine. The first reading of systolic blood pressure obtained with the Doppler machine was an excellent predictor of the mean of five readings, but this was not so for the oscillometric machine. It took less than 5 min to obtain five readings in 37.5% of cases with the Doppler machine but this was true for only 5% of cases with the oscillometric machine. Two cats with ophthalmological lesions consistent with systemic hypertension were identified. In these two patients, systolic blood pressure measurements were between 200 and 225 mmHg when measured by Doppler, and between 140 and 150 mmHg when measured by the oscillometric machine. This suggests that a lower reference range for normal systolic blood pressure values should be used for the oscillometric device.

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.

Plasma Asymmetric Dimethylarginine, Symmetric Dimethylarginine, l‐Arginine, and Nitrite/Nitrate Concentrations in Cats with Chronic Kidney Disease and Hypertension

BACKGROUND Chronic kidney disease (CKD) and hypertension have been associated with decreased bioavailability of nitric oxide (NO) and endothelial dysfunction. Increased concentrations of the endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) are implicated. HYPOTHESIS Plasma ADMA concentration is increased in cats with CKD and systemic hypertension corresponding to a decrease in total plasma nitrate/nitrite (NOx) availability. Decrease in systolic blood pressure (SBP) and proteinuria during treatment of hypertension with amlodipine besylate may be associated with increased NOx availability. ANIMALS Sixty-nine client-owned normotensive and hypertensive cats with variable azotemia. METHODS Plasma ADMA, symmetric dimethylarginine (SDMA), and l-arginine were measured simultaneously by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry in cats from 6 groups: normotensive nonazotemic (n = 10), normotensive mildly azotemic (n = 10), hypertensive mildly azotemic with hypertensive retinopathy (n = 20), hypertensive mildly azotemic without hypertensive retinopathy (n = 10), normotensive moderately azotemic cats (n = 10), and hypertensive nonazotemic cats (n = 9). Plasma NOx concentrations were measured. RESULTS A moderate correlation between plasma creatinine and ADMA (n = 69, r= .608, P < .001), SDMA (n = 69, r= .741, P < .001), and NOx concentrations (n = 69, r= .589, P < .001) was observed. There was no association among plasma ADMA, SDMA, and NOx concentrations and SBP. CONCLUSIONS AND CLINICAL IMPORTANCE Plasma ADMA and SDMA concentrations are increased in cats with CKD and correlate with plasma creatinine concentration. This may imply the presence of endothelial dysfunction in cats with CKD. Plasma ADMA concentrations were not associated with systemic hypertension. Treatment of systemic hypertension with amlodipine besylate did not affect plasma ADMA or NOx concentrations.

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age. Hypothesis/Objectives To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension. Animals/Subjects Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified. Methods Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined. Results Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension. Conclusions and Clinical Importance The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.

Assessment of urinary N-acetyl-β-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.

Plasma renin activity and aldosterone concentrations in hypertensive cats with and without azotemia and in response to treatment with amlodipine besylate

Background Role of renin‐angiotensin aldosterone system (RAAS) in feline systemic hypertension is poorly understood. Objectives Examine plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in normotensive and hypertensive cats with variable renal function and in response to antihypertensive therapy. Animals One hundred and ninety‐six cats >9 years from first opinion practice. Methods PRA, PAC, and aldosterone‐to‐renin ratio (ARR) were evaluated in cats recruited prospectively and grouped according to systolic blood pressure (SBP) and renal function (nonazotemic normotensive [Non‐Azo‐NT], nonazotemic hypertensive [Non‐Azo‐HT], azotemic normotensive [Azo‐NT], azotemic hypertensive [Azo‐HT]). Changes in PRA and PAC were evaluated with antihypertensive therapy (amlodipine besylate). Results Plasma renin activity (ng/mL/h; P = .0013), PAC (pg/mL; P < .001), and ARR (P = 0.0062) differed significantly among groups. PRA (ng/mL/h) was significantly lower in hypertensive (Non‐Azo‐HT; n = 25, median 0.22 [25th percentile 0.09, 75th percentile 0.39], Azo‐HT; n = 44, 0.33 [0.15, 0.48]) compared with Non‐Azo‐NT cats (n = 57, 0.52 [0.28, 1.02]). Azo‐HT cats had significantly higher PAC (n = 22, 149.8 [103.1, 228.7]) than normotensive cats (Non‐Azo‐NT; n = 26, 45.4 [19.6, 65.0], Azo‐NT; n = 18, 84.1 [38.6, 137.8]). ARR was significantly higher in Azo‐HT (n = 20, 503.8 [298.8, 1511]) than Azo‐NT cats (n = 16, 97.8 [77.0, 496.4]). Significant increase in PRA was documented with antihypertensive therapy (pretreatment [n = 20] 0.32 [0.15–0.46], posttreatment 0.54 [0.28, 1.51]), but PAC did not change. Conclusions and Clinical Importance Hypertensive cats demonstrate significantly increased PAC with decreased PRA. PRA significantly increases with antihypertensive therapy. Additional work is required to determine the role of plasma aldosterone concentration in the pathogenesis of hypertension and whether this relates to autonomous production or activation of RAAS without demonstrable increase in PRA.

Psychometric Validation of a General Health Quality of Life Tool for Cats Used to Compare Healthy Cats and Cats with Chronic Kidney Disease.

Background Numerous validated psychometric tools are available to assess impact of disease on a humans quality of life (QoL). To date, no psychometrically validated general health‐related QoL tool exists for cats. Hypothesis/Objectives To develop and validate a tool for assessment of owner‐perceived QoL in cats (CatQoL) and to use this tool to compare QoL between healthy cats and those with chronic kidney disease (CKD). Animals/Subjects Total of 204 owners of young healthy cats (YH, n = 99; <9 years), older healthy cats (OH, n = 35), and cats diagnosed with CKD (CKD, n = 70) completed the CatQoL. Methods Discussions with a focus group and 2 pilot surveys informed design of 16 QoL questions grouped into 4 domains. Each item scored according to frequency and importance, and item‐weighted‐impact‐scores were calculated. The validity of the tool was assessed using principal components analysis and Cronbachs α. The average item‐weighted‐impact‐score (AWIS) was compared among groups and domains. Results Sixteen‐item CatQoL showed good internal consistency reliability (Cronbachs α, 0.77) and unidimensionality with significant loadings (0.2–0.7) and communalities (>0.3). Young healthy cats had significantly higher AWIS (median [IQR], 1.25 [0.63, 1.88]) than OH (0.56 [−0.06, 1.00]) and CKD cats (−0.06 [−0.81, 0.88]), P < .001). CKD cats had significantly lower AWIS for eating domain (YH: 2.00 [1.00, 3.00]; OH: 2.00 [0.67, 3.00]; CKD : 1.00 [0.00, 2.67]) when compared with the YH group and OH group, and all groups differed significantly in their management domain (YH: −0.50 [−1.00, 0.00]; OH: −1.00 [−1.88, −0.50]; CKD : −1.50 [−2.50, −1.00], P < .001). Conclusions and Clinical Importance The CatQoL was validated for use in cats, and can be used as additional assessment parameter in clinical and research settings.

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.

ISFM Consensus Guidelines on the Diagnosis and Management of Hypertension in Cats

Practical relevance: Feline hypertension is a common disease in older cats that is frequently diagnosed in association with other diseases such as chronic kidney disease and hyperthyroidism (so-called secondary hypertension), although some cases of apparent primary hypertension are also reported. The clinical consequences of hypertension can be severe, related to ‘target organ damage’ (eye, heart and vasculature, brain and kidneys), and early diagnosis followed by appropriate therapeutic management should help reduce the morbidity associated with this condition. Clinical challenges: Despite being a common disease, routine blood pressure (BP) monitoring is generally performed infrequently, probably leading to underdiagnosis of feline hypertension in clinical practice. There is a need to: (i) ensure BP is measured as accurately as possible with a reproducible technique; (ii) identify and monitor patients at risk of developing hypertension; (iii) establish appropriate criteria for therapeutic intervention; and (iv) establish appropriate therapeutic targets. Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals. Some cats require long-term adjuvant therapy and, occasionally, additional therapy is necessary for emergency management of hypertensive crises. Evidence base: These Guidelines from the International Society of Feline Medicine (ISFM) are based on a comprehensive review of the currently available literature, and are aimed at providing practical recommendations to address the challenges of feline hypertension for veterinarians. There are many areas where more data is required which, in the future, will serve to confirm or modify some of the recommendations in these Guidelines.