Dominique Paepe

Routine Health Screening: Findings in apparently healthy middle-aged and old cats

Study rationale: Veterinary practitioners often perform geriatric health screening in cats. Unfortunately, scientific information regarding clinical and laboratory abnormalities and normal blood pressure values in elderly cats is scarce. This prospective study evaluated routine health screening tests in apparently healthy middle-aged and old cats. Protocol: One hundred cats of 6 years and older underwent blood pressure measurement, physical examination, blood and urine analysis, indirect fundoscopy and bilateral Schirmer tear tests. Findings: Mean systolic blood pressure (SBP) was 133.6 ± 21.5 mmHg. Increased SBP (>160 mmHg) was observed in eight cats, submandibular lymphadenopathy in 32, gingivitis in 72, heart murmur in 11, thyroid goitre in 20, increased creatinine in 29, hyperglycaemia in 25, increased total thyroxine in three, feline immunodeficiency virus positivity in 14, crystalluria in 41, borderline proteinuria in 25 and overt proteinuria in two. Mean tear production was very similar for both eyes and none of the cats had ocular lesions secondary to hypertension. Clinical significance: Old cats (>10 years) had significantly higher SBP, heart rate, murmur frequency, thrombocyte count, urine protein:creatinine ratio and serum urea and bilirubin concentrations, and significantly lower body condition score, haematocrit, albumin and total calcium concentrations than middle-aged cats (6–10 years). The common occurrence of physical examination and laboratory abnormalities in apparently healthy old cats underlines the need for regular health checks and the development of age-dependent laboratory reference intervals.

Cystatin C: A New Renal Marker and Its Potential Use in Small Animal Medicine

The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time‐consuming and labor‐intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine.

Ultrasonography of the feline kidney: Technique, anatomy and changes associated with disease.

Practical relevance: Ultrasonography is an important tool for the detection of kidney disorders, which are among the most common health problems suffered by cats. It is more accurate than radiography for this purpose and is considered to be the reference modality for imaging the feline kidney, providing excellent visualisation of renal size, shape and internal architecture. Compared with more advanced imaging modalities, such as computed tomography or magnetic resonance imaging, ultrasonography is more accessible, less expensive, does not require general anaesthesia and allows real-time procedures to be performed. Clinical challenges: On ultrasound examination, focal or multifocal disorders may be readily identified, but diffuse changes are more challenging. B-mode ultrasonography is of limited use for differentiating between benign and malignant focal lesions. However, based on the presence and pattern of vascularity as an indicator of malignancy, contrast-enhanced ultrasonography allows distinction between benign and malignant focal renal lesions. Audience: This review provides a framework for the ultrasonographic approach to feline renal and perirenal disorders for the general practitioner. Evidence base: Drawing on current literature relating to ultrasonographic examination of feline kidneys, the aim is to summarise ultrasonographic technique, anatomy and changes associated with renal and perirenal diseases.

Within- and between-examiner agreement for two thyroid palpation techniques in healthy and hyperthyroid cats

Thyroid gland palpation is an important aid for diagnosing feline hyperthyroidism in an early stage to prevent development of deleterious complications. Our objectives were to assess within- and between-examiner agreement for two thyroid gland palpation techniques in cats and to correlate palpation results with ultrasonographic thyroid measurements. Nine client-owned hyperthyroid (12.6±2.4 years) and 10 healthy control cats (7.4±5.4 years) entered this prospective study. Both thyroid glands of all cats were palpated twice by three blindfolded clinicians with the classic palpation technique [technique 1 (T1)] and the technique described by Norsworthy GD, Adams VJ, McElhaney MR, Milios JA [(2002a) Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism. Journal of Feline Medicine and Surgery 4, 139–143] [technique 2 (T2)]. A semi-quantitative score from 1 to 6 was assigned to the gland size. After clipping of the ventral cervical region, another palpation session followed by ultrasonography of the thyroid glands was performed. Average weighted κ-values within- and between-examiners were 0.864 and 0.644 for T1 and 0.732 and 0.532 for T2. T1 did lead to significantly smaller within- (P=0.007) and between-examiner (P=0.048) differences than T2. Significant correlation coefficients (P<0.001) between the palpation scores of both techniques and ultrasonographic thyroid lobe length (T1: 0.43; T2: 0.38) were observed. No significant difference before and after clipping was found (T1: P=0.503; T2: P=0.607). The first time that all cats were palpated by either technique, significant score differences between control and hyperthyroid cats were observed both for T1 (P=0.002) and T2 (P=0.003). Both feline thyroid gland palpation techniques have good within- and between-examiner agreements. Based on this study, the classic palpation technique is preferred.

Biological validation of feline serum cystatin C: The effect of breed, age and sex and establishment of a reference interval

Chronic kidney disease (CKD) is common in cats, but the routine renal markers, serum creatinine (sCr) and urea, are not sensitive or specific enough to detect early CKD. Serum cystatin C (sCysC) has advantages over sCr, both in humans and dogs, and sCysC concentration is significantly higher in cats with CKD than in healthy cats. The objective of this study was to determine the effect of age, sex and breed on feline sCysC and to establish a reference interval for feline sCysC. In total, 130 healthy cats aged 1-16 years were included. sCysC was determined using a validated particle-enhanced nephelometric immunoassay. sCr, urea, urine specific gravity, urinary protein:creatinine ratio (UPC) and systolic blood pressure (SBP) were also measured. No significant differences in sCysC concentration were observed among young, middle-aged and geriatric cats, female intact, female neutered cats, male intact and male neutered cats, or among purebred and domestic short-or longhaired cats. The 95% reference interval for feline sCysC was determined to be 0.58-1.95 mg/L. sCr was significantly higher in geriatric cats than young cats. Serum urea in geriatric cats was significantly higher than in middle-aged and young cats (P = 0.004 and P <0.001, respectively). SBP in geriatric cats was significantly higher than in both middle-aged and young cats (P = 0.004 and P = 0.040, respectively). Male neutered and female neutered cats had significantly higher serum urea concentrations than female intact cats (P = 0.003 and P = 0.006, respectively). Male intact cats had a significantly higher UPC than female intact and female neutered cats (P = 0.02 for each comparison). There were no significant differences among sex groups for USG. It is of concern that sCysC in the majority of cats with CKD in previous studies falls within the reference interval calculated in this study. Further studies are warranted to evaluate the diagnostic value of sCysC as a renal marker in cats.

Analytical validation of a human particle-enhanced nephelometric assay for cystatin C measurement in feline serum and urine

BACKGROUND In people and dogs, Cystatin C (CysC), a renal glomerular and tubular marker, seems superior to serum creatinine to estimate the glomerular filtration rate (GFR). A particle-enhanced nephelometric immunoassay is available to measure human CysC, but there are no reports in cats. OBJECTIVE The goal of this study was the validation of the human CysC nephelometric assay with feline serum and urine, and to perform a pilot study comparing serum and urine CysC between healthy cats and cats with chronic kidney disease (CKD). METHODS Western blot analysis was used to assess cross-reactivity between the polyclonal rabbit anti-human CysC antibody and feline CysC. Imprecision and linearity were determined for feline serum and urine CysC. Serum and urine CysC were measured in 10 healthy and 10 CKD cats. RESULTS Cross-reactivity between the polyclonal rabbit anti-human CysC antibody and feline CysC was demonstrated. Intra- and inter-assay coefficients of variation in feline serum and urine were 1.3% and 0.4%, and 12.5%, and 4.1%, respectively. Cats with CKD had a significantly higher serum CysC concentration (1.24 [0.63-2.99] vs 0.79 [0.43-1.05] mg/L; P = .02) and urine CysC/urinary Creatinine (uCr) ratio (565.6 [0-1311] vs < 0.049/uCr mg/mol; P = .005) compared with healthy cats. CONCLUSIONS The human nephelometric assay showed satisfactory validation results for feline CysC. Cats with CKD had a significantly higher sCysC concentration and uCysC/uCr ratio compared with healthy cats. Additional studies are necessary to evaluate CysC as an early marker of renal damage in cats.

Feline CKD: Diagnosis, staging and screening - what is recommended?

Practical relevance: Feline chronic kidney disease (CKD) is frequently encountered by veterinarians. Timely diagnosis and staging may facilitate the initiation of adequate therapy and improve the prognosis for patients. Clinical challenges: Feline CKD is diagnosed based on the presence of compatible clinical signs and renal azotaemia, which implies that urinalysis (particularly urine specific gravity) is mandatory to confirm the diagnosis. Although the diagnosis of advanced feline CKD and associated complications is usually straightforward, based on complete blood and urine examination, all routine blood and urine tests have their limitations in detecting early CKD. Therefore, diagnosing early or non-azotaemic CKD is much more challenging. Although determination of glomerular filtration rate (GFR) would be ideal to identify early kidney dysfunction, practical limitations hamper its routine use in clinical practice. Patient group: CKD is typically a disease of aged cats, but may affect cats of all ages. Conclusive breed and sex predispositions for feline CKD are not reported. Audience: This review is directed at practising veterinarians and provides an overview of the required diagnostic tests, the classification system established by the International Renal Interest Society, and the importance of and possible techniques for early detection of CKD. Evidence base: Staging of cats with CKD is essential as it directs management and provides a prognostic guide. Given that diagnosis at early disease stages is associated with more prolonged survival times, simple, inexpensive and accurate methods for early CKD diagnosis are needed. Techniques currently under investigation include limited sampling strategies to estimate GFR, clearance marker cut-off concentrations to identify cats with low GFR, new indirect GFR markers and urinary biomarkers.

Prospective evaluation of healthy Ragdoll cats for chronic kidney disease by routine laboratory parameters and ultrasonography

Ragdoll breeder organisations often forewarn Ragdoll cat owners that renal problems may develop as a result of polycystic kidney disease (PKD), chronic interstitial nephritis, familial renal dysplasia or nephrocalcinosis. Healthy Ragdoll and non-Ragdoll cats were prospectively evaluated by measuring serum creatinine and urea concentrations, routine urinalysis and abdominal ultrasonography. All Ragdoll cats also underwent genetic PKD testing. One hundred and thirty-three Ragdoll and 62 control cats were included. Ragdoll cats had significantly lower serum urea concentrations and higher urinary specific gravity. However, median creatinine concentration, median urinary protein-to-creatinine ratio, and the proportion of cats with serum creatinine or urea concentration exceeding the reference interval did not differ. One or more renal ultrasonographical changes were detected in 66/133 (49.6%) Ragdoll and in 25/62 (40%) control cats. Ragdoll cats showed significantly more frequent segmental cortical lesions (7.5% versus 0%), abnormal renal capsule (19.5% versus 8%) and echogenic urine (51.9% versus 25.8%). Chronic kidney disease (CKD) was ultrasonographically suspected in 7/133 (5.3%) Ragdoll and in none of the control cats, which approached significance. Laboratory parameters confirmed kidney dysfunction only in 1/7 of these Ragdoll cats. All Ragdoll cats were PKD negative. In conclusion, first, breed-specific serum creatinine reference intervals are not likely required for Ragdoll cats. Second, renal ultrasonographical abnormalities are common, both in Ragdoll and non-Ragdoll cats. Third, healthy young Ragdoll cats are uncommonly affected by PKD and CKD, but an increased susceptibility of Ragdoll cats to develop CKD cannot be excluded. Finally, Ragdoll cats are predisposed to segmental cortical lesions, which may indicate renal infarction or cortical scarring.

Ultrasonographic appearance of adrenal glands in healthy and sick cats

The first part of the study aimed to describe prospectively the ultrasonographic features of the adrenal glands in 94 healthy cats and 51 chronically sick cats. It confirmed the feasibility of ultrasonography of adrenal glands in healthy and chronically sick cats, which were not statistically different. The typical hypoechoic appearance of the gland surrounded by hyperechoic fat made it recognisable. A sagittal plane of the gland, not in line with the aorta, may be necessary to obtain the largest adrenal measurements. The reference intervals of adrenal measurements were inferred from the values obtained in the healthy and chronically sick cats (mean ± 0.96 SD): adrenal length was 8.9–12.5 mm; cranial height was 3.0–4.8 mm; caudal height was 3.0–4.5 mm. The second part of the study consisted of a retrospective analysis of the ultrasonographic examination of the adrenal glands in cats with adrenal diseases (six had hyperaldosteronism and four had pituitary-dependent hyperadrenocorticism) and a descriptive comparison with the reference features obtained in the control groups from the prospective study. Cats with hyperaldosteronism presented with unilateral severely enlarged adrenal glands. However, a normal contralateral gland did not preclude a contralateral infiltration in benign or malignant adrenal neoplasms. The ultrasonographic appearance of the adrenal glands could not differentiate benign and malignant lesions. The ultrasonographic appearance of pituitary-dependent hyperadrenocorticism was mainly a symmetrical adrenal enlargement; however, a substantial number of cases were within the reference intervals of adrenal size.

Comparison of plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol over a range of glomerular filtration rates expected in cats

The study investigated plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT) and endo-iohexol (PenICT) in six healthy cats, four cats with chronic kidney disease (CKD) and six hyperthyroid (HT) cats to assess potential differences in glomerular filtration rate (GFR) measurement over a wide range of GFR values. The PECCT, PexICT and PenICT were performed in a combined protocol. There was a significant difference between PexICT and PenICT and PECCT in healthy cats. Differences between clearance techniques are suggested to be correlated to range in GFRs and should be taken into account when GFR is measured.