End-stage kidney disease probably due to reflux nephropathy with segmental hypoplasia (Ask-Upmark kidney) in young Boxer dogs in Norway. A retrospective study

This paper is a retrospective morphologic study of 7 young Boxer dogs, showing end-stage kidney lesions compatible with chronic pyelonephritis with severe segmental cortical atrophy and fibrosis, associated with chronic tubulointerstitial inflammation of varying degree. Azotemia was observed in 6 of the 7 cases. The gross kidney lesions were as follows: bilateral small kidneys with numerous segmental cortical scars causing depression of the renal cortical surface. Histologic examination revealed salient atrophy of nephrons, including paucity of glomeruli, glomerulocystic lesions, colloid-filled tubular microcysts, and a conspicuously increased occurrence of arteries with narrowed lumina caused by intimal thickening. These segmental abnormalities were accompanied by pronounced interstitial fibrosis. All but 1 dog showed salient tubulointerstitial lympho-plasmacytic infiltration, which in 3 cases also included diffuse infiltration of polymorphonuclear neutrophilic leukocyte (PMN)-cells and occurrence of tubular PMN-casts. Morphologic signs of abnormal metanephric differentiation (renal dysplasia) were observed in all cases in the form of atypical tubules or asynchronous nephronic development (immature glomeruli) or both. However, other morphologic primary dysplastic features were absent. Based on the morphologic features, it is concluded that the end-stage kidney disease in these young Boxer dogs was the result of chronic atrophic nonobstructive pyelonephritis, most probably caused by vesico-ureteral reflux, compatible with reflux nephropathy causing segmental hypoplasia (Ask-Upmark kidney) in man. It is proposed that atypical tubular epithelium in the form of adenomatoid proliferation of collecting duct epithelial cells should be considered an acquired compensatory lesion, rather than the result of disorganized metanephric development.     

Effects of T lymphocytes, interleukin-1, and interleukin-6 on renal fibrosis in canine end-stage renal disease

Canine end-stage renal disease (ESRD) is defined as the almost complete failure of renal function or irreversible destruction and is characterized by extensive glomerular sclerosis, tubular atrophy, interstitial inflammation, and fibrosis. Renal fibrosis is a common pathway leading to kidney failure. Infiltrating immunocytes in the end-stage kidney and several related factors are involved in renal fibrogenesis. A total of 18 renal tissue samples were obtained from canine patients with ESRD using biopsy and necropsy procedures. The extent of renal fibrosis was histopathologically examined by Masson trichrome staining. T-cell and B-cell localization and macrophage lineages were determined by immunohistochemical staining. Additionally, interleukin-1 (IL-1), IL-2, and IL-6 levels in the canine ESRD kidney were immunohistochemically evaluated and compared with expression patterns in the normal kidney. Significant fibrosis and infiltrating immunocytes consistent with lymphocytes were observed. Although the B-cell count was increased in the end-stage kidney, immunostaining patterns disclosed a marked increase in the number of CD3(+) cells. Furthermore, the remarkable increase in IL-1 and IL-6 levels suggests that T cells in the kidneys of dogs with ESRD spontaneously express these cytokines. In this study, the correlation between the degree of renal fibrosis and cytokines in canine ESRD was examined. The present study shows that T lymphocytes and IL-6 play important roles in renal fibrosis.     

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.     

A Retrospective Analysis of Renal Carcinoma in the Horse

Background: Renal carcinoma is a rare tumor of horses.
Hypothesis: Presenting complaints and clinical signs of this disease are vague and early diagnosis increases survival time.
Animals: Data were collected from the medical records of 4 horses presented to Washington State University as well as the 23 previously published case reports of horses with renal carcinoma.
Methods: Retrospective study.
Results: Renal carcinoma affects horses of all ages with most cases observed in geldings and Thoroughbreds. The most common presenting complaints are nonspecific and usually do not occur until late in the course of the disease. Routine laboratory results generally are unremarkable with no evidence of renal dysfunction. Urine and peritoneal fluid analyses are consistently abnormal, but the changes usually are nonspecific. Rectal palpation often allows detection of an abnormal kidney or a mass in the area of the kidney. Renal ultrasound examination is the most rewarding imaging procedure, and when combined with renal biopsy, antemortem diagnosis can be achieved. Renal carcinoma is both locally invasive and metastatic, necessitating careful staging for metastasis using thoracic radiography and abdominal ultrasound examination. If the tumor is localized to 1 kidney, nephrectomy is the treatment of choice. No chemotherapy or radiation treatment for renal carcinoma has been reported in the horse. Median survival for this series of cases was 11 days (0 days–1 year).
Conclusions and Clinical Importance: Prognosis is poor to grave.     

Renal failure in a pregnant mare

Although chronic renal disease is uncommon in horses, guidelines for management of the broodmare with kidney disease are needed to ensure successful foaling. Herein, we present a case report of a broodmare with chronic renal disease that produced a live foal, and parturition was predicted by monitoring pH and electrolytes in the milk. A 15-year-old pregnant mare presented with a history of poor body condition and weight loss despite an excellent appetite. At presentation, the mare was bright, alert and responsive, with severe pitting ventral oedema and vital parameters within normal limits. Plasma biochemistry revealed azotaemia, hypercalcaemia and hypophosphataemia. Based on clinical ultrasonographic and biochemical parameters, the mare was diagnosed with renal failure. Pregnancy was assessed by transabdominal ultrasound, and the fetal parameters were within normal limits; however, an increased combined thickness of the uterus and placenta and oedematous fetal membranes were found. Monitoring of mammary secretions accurately predicted the onset of foaling at 326 days of gestation. A healthy filly was delivered, and the fetal membranes were passed in a timely manner without complications. Physical examination and haematological parameters were within the normal limits for a neonate foal, except for a mild elevation in blood urea nitrogen. Two weeks later, the mare was subjected to euthanasia due to worsening of her condition. At necropsy and on histopathological examination, the findings were consistent with chronic renal disease. This case demonstrates that a pregnant horse with chronic renal disease can be managed with supportive care and produce a viable foal. Fetal well-being and mare’s prefoaling milk electrolytes were similar to parameters measured in healthy pregnant mares, suggesting that the feto-placental unit may be spared of the dam’s systemic disease. Prepartum physiological changes in the milk may be unaltered with concurrent maternal renal disease and still be useful for foaling prediction.     

Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995

Clinical and laboratory findings at the time of first diagnosis in 80 cats with chronic renal failure (CRF) were examined in a prospective study to determine the survival time of these animals and identify possible factors contributing to the progression of feline CRF. On the basis of clinical presentation, animals were assigned to one of three groups; compensated (n=15), uraemic (n=39) and end-stage (n=26) CRF. Loss of renal concentrating ability was a common finding, even before clinical signs of renal disease were evident. The plasma creatinine concentration at initial presentation was a poor predictor of survival time and the presence of significant anaemia was indicative of a poor prognosis. The study demonstrated the highly variable degree of renal impairment present at the time of diagnosis and the potentially long survival time of many compensated and uraemic cases.     

Progression of chronic renal disease in the dog

Progressive loss of nephron function may be caused by persistence of factors that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical level. Original theories on mechanisms of self-perpetuated nephron injury focused on intraglomerular hypertension and glomerular hypertrophy, but several other factors have now been incriminated, including tubulointerstitial responses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have allowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. Data from these studies indicate that self-perpetuated renal injury is initiated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s), it is likely that self-perpetuated nephron damage is occurring before or at the time when most cases of chronic renal disease are diagnosed. In dogs with remnant kidneys, loss of renal function often occurs at a linear rate over time, but non-linear patterns are common as well. The reciprocal of plasma creatinine concentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease should not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GFR, casting doubt on importance of proteinuria in causing progression of renal disease. However, progressive increases in UPC may be a marker of an accelerated rate of renal injury. Self-perpetuation of renal injury in dogs could be the sole mechanism by which naturally occurring renal diseases progress. When more information is available on the rate of progression of naturally occurring diseases, it may become apparent whether factors initially inciting renal damage have an additive effect on rate of progression.     

Scintigraphic, sonographic, and histologic evaluation of renal autotransplantation in cats.

OBJECTIVE: To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats. ANIMALS: 7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old. PROCEDURE: Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy. RESULTS: By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney. CONCLUSIONS: Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation. CLINICAL RELEVANCE: Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value.     

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.     

Disseminated Mycobacterium paratuberculosis infection in a cow

A cow with chronic diarrhea and weight loss caused by localization of Mycobacterium paratuberculosis in the intestinal tract (Johne's disease) had gross and microscopic changes indicative of a disseminated infection. A direct association between the remote lesions and the intestinal infection was shown by isolation of M paratuberculosis from renal tissue, detection of intracellular M paratuberculosis antigen(s), using an indirect immunoperoxidase method, and by the characteristic granulomatous nature of the lesions. This case illustrates the potential for extra-intestinal lesions in M paratuberculosis infection of cattle and should cause veterinarians to consider mycobacterial disease when confronted with multinodular lesions of the bovine kidney. The immunoperoxidase method was useful in determining the cause of the inflammatory lesion in which intact organisms were not evident.     

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.     

Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat

In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine‐specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.     

Perinephric pseudocysts in the cat: a retrospective study and review of the literature

Perinephric pseudocysts (PNPs) are fluid-filled fibrous sacs that surround the kidney and are not lined by an epithelium. In cats, PNPs are idiopathic, but they usually occur in association with chronic renal failure (CRF). Thirteen cats with PNPs were examined. PNPs occurred in mixed breed cats of either sex with a median age of 16 years. The PNP was palpable on physical examination and usually was interpreted as renomegaly. Clinicopathologic findings reflected CRF, and urinary tract infection was common. Rarely, a primary renal disease was diagnosed concurrent with PNPs and CRF. Diagnosis of PNPs was made by ultrasound examination and fine-needle aspiration, and treatment was by surgical removal of the PNP or ultrasound-guided drainage. Compared to previous reports of PNPs, this series of cats tended to be older and no sex predilection was found, but other findings were similar to those in the literature. Cats with PNPs may have a favorable prognosis if CRF is not severe and no other concurrent diseases are present.     

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.     

Proteinuria: measurement and interpretation

Proteinuria is a general term that describes the presence of any type of protein in the urine (e.g., albumin, globulins, mucoproteins, and Bence-Jones proteins); however, albumin is the predominate protein in urine in healthy dogs and cats as well as dogs and cats with renal disease. Proteinuria can arise from several different physiologic and pathologic causes, but persistent proteinuria associated with normal urine sediment is consistent with kidney disease. The urine dipstick colorimetric test is the usual first-line screening test for the detection of proteinuria, but false-positive reactions are common. When proteinuria of renal origin is suspected, the next diagnostic steps are quantitation and longitudinal monitoring via the urine protein/creatinine ratio. The recent availability of a species-specific albumin enzyme-linked immunosorbent assay technology that enables detection of low concentrations of canine and feline albuminuria has both increased diagnostic capability and stimulated discussion about what level of proteinuria/albuminuria is normal. Beyond being an important diagnostic marker, proteinuria is associated with kidney disease progression in both dogs and cats: the greater the magnitude of the proteinuria, the greater the risk of renal disease progression and mortality. Treatments that have attenuated proteinuria in dogs and cats have also been associated with slowed kidney disease progression and/or improved survival. For these reasons, screening for renal proteinuria and longitudinal assessment of renal proteinuria has recently received renewed interest.     

ULTRASONOGRAPHIC FINDINGS IN CAIRN TERRIERS WITH PRECLINICAL RENAL DYSPLASIA

Renal dysplasia is a hereditary disease characterized by abnormal differentiation of renal tissue. The ultrasonographic appearance of dysplastic canine kidneys has been reported in the late stage of the disease where inflammatory and degenerative changes are already present and the dogs are in chronic renal failure. In this study, we describe the ultrasonographic appearance of the kidneys of five related Cairn Terriers affected with renal dysplasia before the onset of clinical or laboratory evidence of renal failure. Common findings included poor corticomedullary definition and multifocal hyperechoic speckles in the renal medulla, or a diffusely hyperechoic medulla. Severity of ultrasonographic changes was related to the severity of histopathologic findings. The ability to detect dysplastic changes before clinical signs develop makes ultrasound a potentially useful screening method for canine renal dysplasia.     

Bilateral multiple cystic kidney disease and renal cortical abscess in a Boerboel

Cystic renal disease is rare in dogs and although infected renal cysts have been reported in humans, no report could be found in dogs. A 58 kg, 5-year-old, castrated, male Boerboel presented with weight loss, pyrexia, lethargy and vomiting, 20 months after an incident of haematuria was reported. The initial ultrasonographic diagnosis was bilateral multiple renal cysts of unknown aetiology. The cysts had significantly increased in size over the 20-month period and some contained echogenic specks which could be related to infection, normal cellular debris or haemorrhage. In both kidneys the renal contours were distorted (the left more than the right). The abnormal shape of the left kidney was largely due to multiple cysts and a large crescent-shaped septate mass on the cranial pole of the kidney. Aspirates of the septate mass were performed (left kidney) and the cytology and culture were indicative of an abscess. It is suggested that the previous incident of haematuria provided a portal of entry for bacteria into the cysts resulting in renal cortical abscess formation.     

The new age of renal biomarkers: does SDMA solve all of our problems?

Within clinical small animal practice, diagnosis of both chronic kidney disease and acute kidney injury is common. To assess renal function, measurement of glomerular filtration rate is considered the gold standard. Currently, routine tests of kidney function include surrogate markers of glomerular filtration rate such as serum creatinine, and urea, each with their own limitations, whilst urine protein to creatinine ratio gives an indication of glomerular and tubular handling of protein, and urine specific gravity information about urine concentrating ability by the kidney. These parameters are used together with historical and physical examination data to give a diagnosis of kidney disease following which creatinine, proteinuria and blood pressure are used to stage chronic kidney disease and, together with urine output, grade acute kidney injury according to the International Renal Interest Society. However, there has been much concern that creatinine is insensitive when used to indicate early decline in renal function and this has highlighted the need for additional methods of diagnosing and monitoring these patients, with the potential to allow earlier therapeutic intervention. Symmetric dimethylarginine is a novel biomarker, which has been shown to perform as a surrogate marker of glomerular filtration rate in small animals. This article will review current research on symmetric dimethylarginine and the ways in which it may be utilised in small animal practice; current research supports the use of symmetric dimethylarginine as a screening test for detection of early chronic kidney disease according to International Renal Interest Society guidelines, but further research is required in to the usefulness of symmetric dimethylarginine as a tool for monitoring disease and the effect of non-renal influences.     

Early detection of renal damage and disease in dogs and cats.

Renal damage and disease can be caused by acute or chronic insults to the kidney. Acute renal damage often results from ischemic or toxic insults and usually affects the tubular portion of the nephron. In contrast, chronic renal disease can be caused by diseases and/or disorders that affect any portion of the nephron, including its blood supply and supporting interstitium.Early detection of acute renal disease facilitates appropriate intervention that can arrest or at least attenuate tubular cell damage and the development of established acute renal failure. Similarly,early detection of chronic renal disease, before the onset of renal azotemia and chronic renal failure, should facilitate appropriate intervention that stabilizes renal function or at least slows its progressive decline.     

16例犬钩端螺旋体病例的回顾性分析

为了解犬钩端螺旋体病的临床特点和诊疗方法,对2017年10月至2018年7月在浙江大学动物医院确诊的16例钩端螺旋体病犬的发病和诊疗情况进行了回顾分析。PCR诊断钩端螺旋体免疫的公犬是高发群体,雨水较多的月份发病率高于雨水少的月份,由于周边地区金毛、贵宾和田园犬的保有量相对其他品种要高,故在患犬中占比较高。病初主要表现为呕吐、脱水、精神委靡、结膜潮红、食欲废绝等症状。临床检查发现血尿素氮、血肌酐、血磷等指标明显升高,白细胞不同程度升高,部分病例出现贫血。B超检查可见肾肿大、肾实质损伤。主要酸碱紊乱类型为代谢性酸中毒和呼吸性酸中毒,低钠血症最为常见,并发症有肝损伤、胰腺炎、肺炎等。