Prevalence of IgG antibodies to Encephalitozoon cuniculi and Toxoplasma gondii in cats with and without chronic kidney disease from Virginia

Kidney disease is a common and serious condition in domestic cats. There are numerous causes of kidney disease including parasitic infection. Encephalitozoon cuniculi is a microsporidian parasite that develops in the kidneys of rabbits and causes chronic renal disease. Little has been reported concerning E. cuniculi in cats and no serological studies on this parasite in cats have been conducted in the United States to date. The present study explored the possibility that E. cuniculi is an unrecognized contributor to the high prevalence of kidney disease observed in cats. A serological survey was conducted to determine the prevalence of IgG antibodies to spores of E. cuniculi in cats with and without a diagnosis of chronic kidney disease (CKD) according to the International Renal Interest Society (IRIS) staging system. Likewise, samples were examined for IgG antibodies to Toxoplasma gondii, a common well studied protozoan of cats. Plasma and sera were obtained from 232 feline patients at the Virginia-Maryland Regional College of Veterinary Medicine teaching hospital. With the investigators blinded to the renal status of test subjects, samples were screened via indirect immunofluorescent antibody assay (IFA). Thirty-six of the 232 cats met the IRIS staging system criteria for CKD. Antibodies to E. cuniculi were found in 15 of the 232 samples, which included 4 of the 36 cats with CKD. Sera from cats serologically positive to E. cuniculi did not react to spores of E. intestinalis or E. hellem when examined in the IFA. Antibodies to T. gondii were found in 63 of the 232 samples, which included 10 of the 36 cats with CKD. The prevalence of antibodies in cats with CKD to either protozoan was not significantly different (P>0.05) from the cats without CKD in the study. Collectively the results do not support the hypothesis that either E. cuniculi or T. gondii play a significant etiologic role in the occurrence or progression of CKD in cats.     

Comparative study of chronic kidney disease in dogs and cats: Induction of myofibroblasts

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, α-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The α-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.     

Preliminary study of urinary excretion of liver-type fatty acid-binding protein in a cat model of chronic kidney disease

Urinary liver-type fatty acid-binding protein (uL-FABP) is a clinically useful biomarker for monitoring chronic kidney disease (CKD) in humans. However, long-term monitoring of uL-FABP in CKD cats has not been reported. The objective of this preliminary study was to investigate whether the urinary excretion of L-FABP could predict the deterioration of renal function in 2 CKD model cats. Urinary liver-type fatty acid-binding protein (uL-FABP) increased before standard renal biomarkers, including serum creatinine, blood urea nitrogen, and symmetric dimethylarginine, in 1 cat with deteriorating renal function, but remained low and relatively stable in another cat with stable renal function. Our results suggest that uL-FABP is a potential clinical biomarker for predicting the progression of CKD in cats, as it is in humans.     

Absence of renal cortical anisotropic backscattering artifact in feline chronic kidney disease

Renal cortical anisotropy backscattering artifact (CABA) is a focal hyperechoic region where the tubules are parallel to the incident ultrasound beam, reflecting most of the beams to the transducer. To investigate the association between chronic kidney disease (CKD) and the absence of renal CABA in cats. Ultrasonographic renal images of 40 cats with CKD (stage II-IV) and 36 clinically healthy cats were blindly evaluated by two observers to determine the visibility of renal CABA. Inter- and intraobserver agreements were evaluated using McNemar’s test. The association between the absence of renal CABA and CKD was assessed using Fisher’s exact test. Excellent intraobserver and substantial interobserver agreements were demonstrated. A significant association (P < .0001) between absent renal CABA and CKD stage was revealed in all cats. Cats with CKD had an increased risk of the absence of renal CABA (Odds ratio, 56.0; 95% CI, 13.8–227.0) compared with the clinically healthy cats. The absence of renal CABA revealed 87.5% sensitivity and 88.9% specificity to detect CKD in all cats, and 91.7% sensitivity and 83.3% specificity in aged cats. Our study demonstrated a correlation between feline CKD and the absence of renal CABA, providing a feasible and alternative method for feline CKD evaluation.     

A long term feed supplementation based on phosphate binders in Feline Chronic Kidney Disease

Chronic kidney disease (CKD) is a very common disorder in elderly cats. A proper renal diet represents the most efficient therapeutic intervention to improve survival and life quality in feline patients with 3 and 4 International Renal Interest Society (IRIS) stages. Twenty cats were selected in this study. Ten were administered the dietary supplementation for 360 days and the other ten, whose owners did not give consent for any supplemental therapies apart from the renal diet, were selected from a clinical database and used as control group. The present study is a long term study (360 days) aiming to evaluate the efficacy and palatability of a dietary supplementation containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in cats diagnosed with 3 and 4 IRIS stages of CKD. The owners were asked to fill in questionnaires to get information on the cat’s appetite, the palatability of the given supplement, the presence of vomit and/or diarrhoea, general health and vitality. Hematochemical, biochemical and urinary analyses were performed on day 0, 30, 60, 90, 120, 150,180 and 360. GraphPad Prism® software was used to perform statistical analysis. Our study shows that the given dietary supplement reduced serum phosphorus and increased serum bicarbonate values in cats with CKD. In turn, this supplement could be used as a support therapy in cats with advanced CKD improving their clinical conditions without any adverse reaction. Finally, it is important to underline that all the animals completed the study and the owners reported a good palatability of the feed supplement.     

Contrast‐Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in Cats with Chronic Kidney Disease

Background

Contrast‐enhanced ultrasound examination (CEUS) is a functional imaging technique allowing noninvasive assessment of tissue perfusion. Studies in humans show that the technique holds great potential to be used in the diagnosis of chronic kidney disease (CKD). However, data in veterinary medicine are currently lacking.

Objectives

To evaluate renal perfusion using CEUS in cats with CKD.

Animals

Fourteen client‐owned cats with CKD and 43 healthy control cats.

Methods

Prospective case‐controlled clinical trial using CEUS to evaluate renal perfusion in cats with CKD compared to healthy control cats. Time‐intensity curves were created, and perfusion parameters were calculated using off‐line software. A linear mixed model was used to examine differences between perfusion parameters of cats with CKD and healthy cats.

Results

In cats with CKD, longer time to peak and shorter mean transit times were observed for the renal cortex. In contrast, a shorter time to peak and rise time were seen for the renal medulla. The findings for the renal cortex indicate decreased blood velocity and shorter total duration of enhancement, likely caused by increased vascular resistance in CKD. Increased blood velocity in the renal medulla has not been described before and may be because of a different response to regulatory factors in cortex and medulla.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasound examination was capable of detecting perfusion changes in cats with CKD. Further research is warranted to assess the diagnostic capabilities of CEUS in early stage of the disease process.     

Measurement, interpretation, and implications of proteinuria and albuminuria.

Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats.     

A comparative study of chronic kidney disease in dogs and cats: induction of cyclooxygenases

The present study investigated whether renal cyclooxygenase (COX) induction is associated with the severity of chronic kidney disease (CKD) in dogs and cats. The collected kidneys were examined histopathologically and immunohistochemically. The immunoreactivities of COX-1 and COX-2 were evaluated quantitatively, and the correlations to the plasma creatinine concentrations, glomerular size, glomerulosclerosis, interstitial fibrosis, and interstitial cell infiltration were evaluated statistically. Immunoreactivities for COX-1 were heterogeneously observed in the medullary distal tubules and collecting ducts; no correlations with the severity of renal damage were detected. Immunoreactivities for COX-2 were heterogeneously observed in the macula densa (MD) regions. In dogs, the percentage of COX-2-positive MD was significantly correlated with the glomerular size. In cats, glomeruli with COX-2-positive MD had significantly higher sclerosis scores than those with COX-2-negative MD. In conclusion, renal COX-2 is induced in canine and feline CKD, especially in relation to the glomerular changes.     

Positive correlation between renal tubular flattening and renal tubular injury/interstitial fibrosis in murine kidney disease models

The number of patients with chronic kidney disease (CKD) is growing continuously globally. In order to study pathogenesis and mechanisms, many animal models have been developed, including spontaneous, genetic, and induced models. Although each type of CKD shows disease-specific tissue changes in the early stages, tubular disorder and interstitial fibrosis histologically occur in the course of progression to end-stage renal failure. Therefore, the quantification of tubular disorder and interstitial fibrosis in CKD research using animal models is essential for measuring the degree of CKD severity and, thus, efficacy of therapeutic agents. Several strategies have been used to quantify interstitial fibrosis. Among scoring factors, renal tubular flattening can be quantitatively evaluated easily and inexpensively. However, the diagnostic value of renal tubular flattening evaluation has not been investigated previously. Therefore, in this study, we investigated the correlation between renal tubular flattening and interstitial fibrosis or renal tubular injury markers. We observed a strong correlation between the degree of tubular injury/interstitial fibrosis and renal tubular flattening in three types of mouse renal disease model. This is advantageous because rapidly advancing technologies such as artificial intelligence and image processing can be easily applied; hence, a more precise, objective, and quantitative diagnosis should be possible in the future.     

Prognostic factors in cats with chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD.     

Renal transitional-cell carcinoma in two cats with chronic kidney disease

Two 12-year-old cats were diagnosed with chronic kidney disease (CKD) based on physical examination, clinicopathologic data and, in one case, abdominal ultrasound findings. Approximately 1 year after the initial diagnosis of CKD both cats developed renal transitional cell carcinoma (TCC)--bilateral in one cat. Based on post-mortem examination, one cat had no evidence of metastasis and the other had metastasis to the large intestine, heart and lungs. This is the first report of de novo bilateral renal TCC in a cat, as well as the first report of renal TCC developing in cats with previous history of confirmed CKD.     

猫肥厚型心肌病与心肌纤维化

肥厚型心肌病是猫最常见的原发性心脏疾病,典型特征为心脏左心室肥厚。心肌纤维化是猫肥厚型心肌病的标志性病理变化,其可导致心脏功能障碍和节律异常,是心肌病患猫预后不良的重要因素。对于猫肥厚型心肌病与心肌纤维化,目前缺乏针对性治疗,新型治疗方法亟需开发。本综述总结了猫肥厚型心肌病的病理特征以及目前关于猫心肌纤维化发病机制的研究进展,拟通过探索心肌纤维化的发病机制,从而为猫肥厚型心肌病新型治疗药物的开发寻找突破点。     

Polycystic kidney disease in four British shorthair cats with successful treatment of bacterial cyst infection

Polycystic kidney disease is the most common inherited disorder in cats. Renal cysts progressively increase in size and number, resulting in a gradual decrease in kidney function. An autosomal dominant mutation in exon 29 of the polycystin‐1 gene has been identified, mostly in Persian and Persian‐related breeds. This case study describes polycystic kidney disease in four British shorthair cats, of which two had the same genetic mutation reported in Persian and Persian‐related cats. This likely reflects introduction of this mutation into the British shorthair breeding line because of previous outcrossing with Persian cats. An infected renal cyst was diagnosed and successfully treated in one of the cats. This is a commonly reported complication in human polycystic kidney disease, and to the authors’ knowledge has not previously been reported in cats with polycystic kidney disease.     

Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997)

A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 ± 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 ± 0.4 mg/dL; P <.03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia ( P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.     

Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease

There is a growing body of experimental and clinical evidence supporting mineralocorticoid receptor (MR) activation as a powerful mediator of renal damage in laboratory animals and humans. Multiple pathophysiological mechanisms are proposed, with the strongest evidence supporting aldosterone-induced vasculopathy, exacerbation of oxidative stress and inflammation, and increased growth factor signalling promoting fibroblast proliferation and deranged extracellular matrix homeostasis. Further involvement of the MR is supported by extensive animal model experiments where MR antagonists (such as spironolactone and eplerenone) abrogate renal injury, including ischaemia-induced damage. Additionally, clinical trials have shown MR antagonists to be beneficial in human chronic kidney disease (CKD) in terms of reducing proteinuria and cardiovascular events, though current studies have not evaluated primary end points which allow conclusions to made about whether MR antagonists reduce mortality or slow CKD progression. Although differences between human and feline CKD exist, feline CKD shares many characteristics with human disease including tubulointerstitial fibrosis. This review evaluates the evidence for the role of the MR in renal injury and summarizes the literature concerning aldosterone in feline CKD. MR antagonists may represent a promising therapeutic strategy in feline CKD.     

Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats

Objective-To determine whether a renal diet modified in protein, phosphorus, sodium, and lipid content was superior to an adult maintenance diet in minimizing uremic episodes and mortality rate in cats with stage 2 or 3 chronic kidney disease (CKD). Design-Double-masked, randomized, controlled clinical trial. Animals-45 client-owned cats with spontaneous stage 2 or 3 CKD. Procedures-Cats were randomly assigned to an adult maintenance diet (n = 23 cats) or a renal diet (22) and evaluated trimonthly for up to 24 months. Efficacy of the renal diet, compared with the maintenance diet, in minimizing uremia, renal-related deaths, and all causes of death was evaluated. Results-Serum urea nitrogen concentrations were significantly lower and blood bicarbonate concentrations were significantly higher in the renal diet group at baseline and during the 12- and 24-month intervals. Significant differences were not detected in body weight; Hct; urine protein-to-creatinine ratio; and serum creatinine, potassium, calcium, and parathyroid hormone concentrations. A significantly greater percentage of cats fed the maintenance diet had uremic episodes (26%), compared with cats fed the renal diet (0%). A significant reduction in renal-related deaths but not all causes of death was detected in cats fed the renal diet. Conclusions and Clinical Relevance-The renal diet evaluated in this study was superior to an adult maintenance diet in minimizing uremic episodes and renalrelated deaths in cats with spontaneous stage 2 or 3 CKD.     

Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease

Feline renal diseases are increasingly noted in veterinary practice. It is important to diagnose and identify the pathological basis of renal dysfunction accurately at an early stage, but there are only a few reports on this area in clinical veterinary medicine. We investigated the efficacy of measurement of urinary albumin (u-Alb) and urinary transferrin (u-Tf) for early diagnosis using 5-µl urine samples collected noninvasively by catheterization from normal (IRIS stage I) cats and cats with stage I chronic kidney disease (CKD). The u-Alb levels in normal and stage I CKD cats were 6.0 ± 4.5 and 11.2 ± 8.4 mg/dl, respectively, and the u-Tf levels were 0.09 ± 0.42 and 0.52 ± 0.79 mg/dl, respectively. Based on ROC curve analysis, the sensitivity and specificity of u-Alb and u-Tf were higher than those of the currently used biomarker, the plasma creatinine level. The sensitivity of u-Alb was higher than that of u-Tf, whereas the specificity of u-Tf was higher than that of u-Alb. The validity of the threshold albumin level (20 mg/dl) was confirmed by measurements using SDS-PAGE. Since leakage of u-Tf in urine precedes leakage of u-Alb, inclusion of u-Tf in biochemistry tests may be appropriate for IRIS staging as a diagnostic marker of early diagnosis of renal disorder in cats.     

Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease

The prevalence of urinary tract infections (UTIs) in cats with hyperthyroidism (n=90), diabetes mellitus (DM) (n=57) and chronic kidney disease (CKD) (n=77) was evaluated retrospectively. It was found to be 12% in cats with hyperthyroidism and DM, respectively, and 22% in cats with CKD. Associations between UTIs and clinical signs, biochemical markers in serum and urinalyses were investigated. Many of the cats with UTIs had no clinical signs of lower urinary tract disease or changes in their laboratory values indicative of infection. Therefore, a urinalysis alone should not be used to exclude UTIs in these cats. UTIs are relatively common in cats with hyperthyroidism, DM and CKD, and urine cultures are recommended as part of the basic diagnostic plan for cats suspected of suffering from these conditions.     

Resolution of renal adenocarcinoma-induced secondary inappropriate polycythaemia after nephrectomy in two cats

Two cases of secondary, inappropriate polycythaemia caused by renal adenocarcinoma in domestic shorthair cats, are described. The cats were 9 and 12 years old and both were presented because of generalised seizures presumably due to hyperviscosity. Both cats had a markedly increased haematocrit (0.770 and 0.632 l/l) and thrombocytosis (744 x 10(9)/l and 926 x 10(9)/l). An abdominal ultrasound revealed a mass in the cranial pole of one kidney in both cats. Serum erythropoietin (EPO) concentration was within the reference interval (RI) in both cats but was inappropriately high considering the markedly increased haematocrit. The cats were initially stabilised and managed by multiple phlebotomies and intravenous fluid therapy and underwent nephrectomy of the affected kidney later on. Both the polycythaemia and thrombocytosis resolved following surgery. Postoperative serum EPO concentration, measured in one cat, decreased markedly. Histopathology of the affected kidneys confirmed a diagnosis of renal adenocarcinoma. Both cats were stable for an 8-month follow-up period; however, one cat had developed a stable chronic kidney disease (CKD), while the other was represented 8 months postoperatively due to dyspnoea, and had radiographic evidence of lung metastasis, presumably because of the spread of the original renal tumour and was euthanased. Initial stabilisation of polycythaemic cats should include multiple phlebotomies. Nephrectomy should be considered in cats with secondary, inappropriate, renal adenocarcinoma-related polycythaemia when only one kidney is affected by the tumour, and provided that the other kidney's function is satisfactory. Nephrectomy should be expected to resolve the polycythaemia and lead to normalisation of serum EPO concentration.