Progressive nephropathy due to renal dysplasia in shih tzu dogs in Sweden: A clinical pathological and genetic study

The clinical and pathological findings in 45 shih tzu dogs with progressive nephropathy due to renal dysplasia are described. There was no sex dependence and the age at death/euthanasia varied from seven weeks to nine years, with a mean age of two years. The most common clinical signs were depression, polydipsia and vomiting. All dogs showed elevated blood urea levels and most passed dilute urine. Proteinuria and anaemia were the most common findings. At necropsy all dogs had small, lobulated, pale kidneys with capsular adhesion. Multiple cysts in the cortex and in the intermediary zone were found in most cases. The morphological changes were three different types based on microscopic examination:

• 1 Primary dysplastic lesions; where fetal glomeruli were the most consistent finding.
• 2 Compensatory changes; where hypertrophy and hyperplasia of the glomerular tufts and tubules were most frequently observed.
• 3 3 Inflammatory lesions and fibrosis were found in all cases.
• 4 A genetic study of 37 dogs suggests a simple recessive mode of inheritance. Based on this information a control scheme against renal dysplasia has been instigated.

     

Familial renal disease in Soft-coated Wheaten Terriers

In two litters of Soft-coated Wheaten Terriers, having the same parents, chronic renal failure developed in five out of ten dogs. The dogs died, or were destroyed on humane grounds, at 7 to 30 months of age. Clinical signs were inappetence, weight loss, vomiting, depression and, in two cases, polydipsia and polyuria. The laboratory data revealed isosthenuria, non-regenerative anaemia, extremely high serum urea nitrogen, and creatinine values. Pathoanatomical findings included small kidneys with an irregular and pale external surface. Cortical lesions were mostly segmental in distribution, and consisted of loss of glomerular elements and increased interstitial connective tissue. Medullary lesions were severe, diffuse in distribution, and consisted of loss of tubules and proliferation of connective tissue. The clinical, laboratory, and pathoanatomical findings show similarities to renal diseases seen in young dogs of other breeds.     

Effects of serial ultrasound-guided renal biopsies on kidneys of healthy adolescent dogs

Ten healthy mixed-breed dogs were used to evaluate the functional and structural effects of serial ultrasound-guided renal biopsies obtained with an automated biopsy needle. In each dog, one lateral renal cortex was biopsied at 2, 4, and 6 months of age; the other kidney was the control. Five dogs had two tissue cores and five dogs had four tissue cores taken on each biopsy occasion, and one core was examined microscopically. One week before each biopsy and a month after the final biopsy, the glomerular filtration rate (GFR) was determined by renal scintigraphy. Dogs were then euthanized for evaluation of gross and microscopic lesions attributable to the biopsies. There was no difference between GFR values for biopsied kidneys and those of control kidneys ( P >0.05). Microscopic lesions were not identified in biopsies taken at 2 and 4 months, but focal lesions were found in three of 10 specimens taken at 6 months of age. At necropsy, six of 10 biopsied kidneys had small visible capsular scars, and linear tracts <2 mm wide were observed on cut surfaces in six of 10 biopsied kidneys cut transversely into slices 5 mm thick. Discrete light microscopic lesions were observed in 25 of 452 (5.5%) of randomly selected 6-mm-diameter sections of renal cortex from biopsied kidneys. We conclude that serial renal cortical biopsies can be obtained by our method from healthy adolescent dogs with minimal risk of inducing changes that might be confused with those of a progressive renal disease.     

Progressive renal disease in Soft-coated Wheaten Terriers: possible familial nephropathy

Clinical and pathological features are described in seven young Soft-coated Wheaten Terriers with chronic renal disease. The oldest dog was 21/2 years; in the other six, ages at death ranged from one to 15 months. Two of the puppies were littermates: one died at 4 weeks, the other at 12 months. Two of the dogs were examined at intervals up to 14 months, during which time there was progressive deterioration in renal function. All seven dogs had abnormal kidneys with cortical narrowing. The histological features were not consistent and included: tubular dilatation and basement membrane thickening; an unusually large proportion of immature glomeruli; persistence of interstitial connective tissue resembling foetal mesenchyme. Inflammatory change was minimal except in two dogs with super-imposed pyelonephritis. The clinical and laboratory data suggest that these dogs had dysplasia of the kidneys that progressed to chronic renal disease during early life. In three dogs there was a familial relationship.     

Canine renal failure syndrome in three dogs

Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7~10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.     

Histological and ultrastructural studies of renal lesions in Babesia canis infected dogs treated with imidocarb

Histological and electron microscopic examinations of the kidneys of 8 dogs suffering from fatal, naturally acquired Babesia canis infection and nephropathy are presented. Seven animals were treated with imidocarb dipropionate on average 4.5 days prior to death. Severe anaemia was present only in 2 cases. Degenerative histological changes observed mostly in the proximal convoluted tubules included vacuolar-hydropic degeneration, necrosis and detachment of renal tubular epithelial (RTE) cells from the basement membrane. Necrotic debris occasionally formed acidophilic casts within the tubules. In some cases, necrosis of the whole tubule was observed. Haemoglobin casts in the tubules and haemoglobin droplets in RTE cells seldom appeared. No significant histological changes were seen in the glomeruli. Ultrastructural lesions in RTE cells included nuclear membrane hyperchromatosis, karyopyknosis, karyolysis, swelling or collapse of mitochondria with fragmentation of cristae and vacuolar-hydropic degeneration in the endoplasmic reticulum and microvilli. Nuclear oedema was also observed. Many RTE cells exhibiting necrosis collapsed. Vacuolar-hydropic degeneration and necrosis were also observed in the glomerular and interstitial capillary endothelium. The severe acute tubular necrosis described in this study is probably the result of hypoxic renal injury. Systemic hypotension leading to vasoconstriction in the kidneys might be the most important cause of renal hypoxia in B. canis infections, but anaemia may also contribute to inadequate oxygenation. Imidocarb should be applied with caution in patients with possible renal involvement until further data become available on its potential nephrotoxicity in dogs.     

Renal pathology in working dogs in the South African National Defence Force

Urine analysis, serum biochemical profile and a cortical wedge biopsy for histopathological examination was performed on 42 South African National Defence Force (SANDF) dogs from around the country. The only significant finding on urine analysis and serum biochemistry was a relatively large number (16/42) of dogs with elevated serum inorganic phosphate levels. Histopathology revealed that only 9 of the animals had normal kidneys reflected in the wedge biopsy material, with over 50% of them showing signs of glomerular pathology (primarily mesangioproliferative glomerulonephritis). Other conditions detected histopathologically were haemosiderosis (47% of animals), focal nephrosis (2.4%), membranoproliferative glomerulonephritis (2.4%), focal interstitial nephritis (4.7%) and acute tubular nephrosis (4.7%). The lesions observed were of limited distribution and extent; this histopathological finding may account for the absence of significant abnormalities on urine analysis or serum biochemistry profiles. It appears from these results that a large percentage of the SANDF population would be expected to have mild renal lesions, but that these lesions are not severe enough to lead to clinical signs. The findings of this study are similar to those of randomly selected populations of non-military dogs performed in other areas of the world, which also demonstrated an unexpectedly high incidence of histopathological renal pathology in dogs considered healthy. These lesions may well, however, play a role in later life, and it is recommended that military veterinarians maintain an index of suspicion for renal disease, particularly glomerular disease. The aetiology of the histopathological lesions is unknown.     

Familial progressive nephropathy in young Bull Terriers

The clinical, clinicopathological and pathological findings are described in three Bull Terrier bitches with advanced renal disease. The bitches were less than four years old and showed variable presenting signs but anorexia, lethargy and polydipsia were the most frequent. All three dogs were azotaemic and isosthenuric. Urinary protein was measured in two of the three cases. Both were proteinuric. At necropsy all dogs had shrunken kidneys. Histological examination revealed nephron loss, atrophy of glomerular tufts, interstitial fibrosis, and mineralisation of basement membranes.

The progressive renal disease in these dogs was similar to the condition reported in Bull Terriers in Australia, and is probably familial and inherited.     

Early effects of ethylene glycol on the ultrastructure of the renal cortex in dogs

A sublethal dose of ethylene glycol was administered orally to 3 groups of dogs; dogs of a control group were given distilled water instead. Renal cortical biopsy samples were obtained from dogs of experimental and control groups at various times after treatment. Tissue was examined by use of light microscopy and transmission electron microscopy. In dogs of the control group, the light and electron microscopic appearances of tissue were within normal limits at all sample collection hours. In dogs of the experimental groups, renal corpuscular structure remained within normal limits by use of light and electron microscopy throughout the study, though morphologic change was seen in other structures of the cortex. Light microscopic lesions first appeared at 12 hours, and were similar to those reported in the literature. Ultrastructural lesions were first observed in the 5-hour samples, and similar to the light microscopic lesions, were most common in the proximal convoluted tubules (PCT). Initial PCT cellular changes included vacuolization of cells and distention of the parabasal extracellular spaces; PCT cellular lesions seen in later-hour samples included formation of apical buds and cellular rupture. Internalization or sloughing of the PCT brush border was not observed. Distal convoluted tubules (DCT) were frequently dilated and/or packed with cellular debris. A few DCT cells had degenerative or necrotic changes. In PCT and DCT, abnormal cells were frequently flanked by normal or nearly normal cells. During later hours, a few cells with types of changes first observed in early hours continued to be observed, implying ongoing response of cells to the toxin.     

The pentobarbital anesthetized dog: an animal model for assessing chemically induced changes in renal function and ultrastructure

An experimental procedure was devised using the pentobarbital-anesthetized dog that could be used for the comprehensive evaluation of the renal effects of chemicals. After IV or renal arterial administration of 0.9% saline solution (vehicle), 12 renal function determinants were continuously monitored for periods of 2 and 6 hours. At the completion of the 2 or 6 hours of study, the kidneys of a number of dogs (usually between 1 and 7) in each vehicle-treated group were subjected to a modification of the intravascular perfusion-of-fixative technique to evaluate the ultrastructural status of the outer cortical, inner cortical, and outer medullary tissue. The remaining dogs (at least 3) in each vehicle-treated group were given a nonnephrotoxic, but maximally effective, diuretic dose of ethacrynic acid, which enabled an assessment of the functional integrity of the thick ascending limb of Henle's loop. Renal function and glomerular and tubular ultrastructure remained stable in the pentobarbital-anesthetized dog for up to 6 hours after administration of vehicle. Sustained infusion of inulin (included in the procedure to estimate glomerular filtration rate) throughout the duration of the experiments, and pentobarbital anesthesia of various durations did not alter the morphologic status of the canine nephron. The procedure used for the renal perfusion of fixative circumvented any manipulation of the kidneys before fixation and allowed for the acquisition of normal (unaltered) appearing tissue from all areas of the kidneys. The responses of pentobarbital-anesthetized dogs to ethacrynic acid administration were similar when given 2 and 6 hours after the vehicle administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Familial renal amyloidosis in Chinese Shar Pei dogs

Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA.     

Mycotoxicosis produced in swine by cultural products of an isolate of Aspergillus ochraceus. I. Clinical observations and pathology.

Pigs fed a ration, 25% of which was rice culture, of Aspergillus ochraceus lost weight or failed to gain and became depressed. Some pigs died and most developed subcutaneous edema, hydrothorax, hydroperitoneum, pulmonary atelectasis, edema of the mesentery and perirenal edema. Microscopic lesions in addition to edema were primarily renal and consisted of tubular degeneration and necrosis, hyaline tubular casts, interstitial fibrosis and tubular cell regeneration. The first change found after 3 days was cytoplasmic vacuolation of the convoluted and straight segments of the proximal tubules. Necrotic proximal tubules were found after 4 days and after 9 days degeneration and necrosis involved predominantly proximal tubular segments. Pigs fed a ration, 12.5% of which was rice culture, for 8 weeks did not develop perirenal edema but had firm kidneys. Extensive interstitial fibrosis of the cortical labyrinth was the principal change. Within the fibrous connective tissue, some tubules were necrotic and others were atrophied.     

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.     

Acute intrinsic renal failure and blood coagulation disorders after a snakebite in a dog

Acute intrinsic renal failure was diagnosed in a two-year-old, male, German shepherd dog following a Vipera aspis bite. Clinical signs included depression, hypersalivation, vomiting, tachypnoea, abdominal pain, splenomegaly, oliguria with haematuria and haemolysed serum. Leucocytosis with a shift to the left, thrombocytopenia, prolonged coagulation times (activated partial thromboplastin time, prothrombin time and thrombin time), hypofibrinogenaemia, azotaemia and hyposthenuria were the most prominent laboratory abnormalities. Histopathological evaluation of the kidneys showed a discrete glomerular hypercellularity, mesangial lysis and renal tubules filled with many hyaline casts and some necrotic cells.     

Outbreaks of renal failure associated with melamine and cyanuric acid in dogs and cats in 2004 and 2007.

Sixteen animals affected in 2 outbreaks of pet food-associated renal failure (2 dogs in 2004; 10 cats and 4 dogs in 2007) were evaluated for histopathologic, toxicologic, and clinicopathologic changes. All 16 animals had clinical and laboratory evidence of uremia, including anorexia, vomiting, lethargy, polyuria, azotemia, and hyperphosphatemia. Where measured, serum hepatic enzyme concentrations were normal in animals from both outbreaks. All animals died or were euthanized because of severe uremia. Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. Crystals and histologic appearance were identical in both outbreaks. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. These results indicate that the pet food-associated renal failure outbreaks in 2004 and 2007 share identical clinical, histologic, and toxicologic findings, providing compelling evidence that they share the same causation.     

Bile duct dysplasia and congenital hepatic fibrosis associated with polycystic kidney (Caroli syndrome) in a rat

Hepatic fibrosis with bile duct ectasia and hyperplasia associated with polycystic kidney disease, analogous to Caroli syndrome in humans, was observed in a rat used as a control in a subchronic toxicity study. Light microscopy of liver sections showed multiple cystic and segmental saccular dilatations and hyperplasia of the intrahepatic bile ducts associated with overgrowth of portal connective tissue; the kidneys had diffuse cystic dilatation of cortical renal tubules. The lesions resembled those of human cases of the fibropolycystic disease termed as Caroli syndrome, which is thought to be the result of a pathologic developmental process known as ductal plate malformation. Recently, an animal model of Caroli syndrome has been described in mutant rats from a colony that constantly showed renal and hepatic cysts and an autosomal recessive mode of inheritance. The finding in our case of identical hepatorenal lesions suggests that the same mutation has occurred incidentally in a standard colony.     

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.     

Renal amyloidosis in related English foxhounds

Renal amyloidosis was diagnosed in six related English foxhounds from two separate hunting kennels. There was no apparent age or sex predilection. All the dogs had clinical and laboratory findings compatible with renal disease. The onset of clinical signs was acute in all cases with death or euthanasia in five of the six affected dogs occurring within one week of presentation. The remaining dog was treated with diuresis which produced a temporary improvement. Histological examination of renal tissue from affected dogs identified the presence of both glomerular and interstitial amyloid, which was confirmed by immunohistochemical staining to be of the reactive type (amyloid A). There were occasional sclerosed glomeruli or glomeruli with thickened Bowman's capsules, in addition to interstitial and periglomerular infiltration with a predominance of plasma cells and lymphocytes and secondary changes including tubular eosinophilic casts. Renal papillary necrosis was identified in three dogs. One hound had concurrent multicentric lymphoma. Pedigree analysis of the affected dogs revealed that four individuals shared a common great grandsire and that the same dog was the grand-sire of a further case. Pedigree analysis of five additional dogs from one of the kennels, all of which had clinical signs of acute renal failure but from which renal tissue was not available, revealed a close relationship to those foxhounds with confirmed renal amyloidosis.     

Glomerulonephropathy in aged captive Key Largo woodrats (Neotoma floridana smalli)

A retrospective review of mortality records of Key Largo woodrats (Neotoma floridana smalli) in a captive breeding program revealed chronic renal disease in 5 of 6 woodrats older than 4 years of age. Two of the 5 woodrats with chronic renal disease also had clinical evidence of diabetes mellitus. Kidneys from all 5 woodrats were examined via light microscopy, histochemical staining, immunohistochemical staining, and transmission electron microscopy. The dietary histories of the affected animals were examined as well. The most striking histopathologic abnormality in the affected kidneys was the presence of large protein casts within cortical and medullary tubules in combination with lesions of membranous glomerulopathy and glomerulosclerosis. Transmission electron microscopy revealed thickening and undulation of the tubular and glomerular mesangial basement membranes with the variable presence of electron-dense deposits within the capillary endothelial basement membrane. Patchy glomerular immunoreactivity for IgG was noted in 2 cases, but IgA and IgM immunoreactivity were not present. The pathologic changes in the kidneys of the Key Largo woodrats mirrored many of the features of chronic progressive nephropathy commonly diagnosed in laboratory rats. Woodrats in the captive population were fed an ad libitum high-protein diet similar to diets that have been shown in laboratory rats to exacerbate the development and progression of chronic progressive nephropathy. It is concluded that Key Largo woodrats develop glomerulonephropathy with features similar to chronic progressive nephropathy described in laboratory rats. Age, concomitant disease, and dietary factors may contribute to the development and severity of this potentially age-limiting disease in Key Largo woodrats.     

CHRONIC RENAL FAILURE IN A YOUNG PONY

SUMMARY A 19-month-old pony gelding was presented with chronic renal failure, after deteriorating progressively during the preceding 3 months. There was pronounced azotaemia, hyponatraemia and hypochloraemia, but plasma calcium and phosphorus levels were normal. At autopsy both kidneys were small and nodular and were characterised by collapsed segments of cortex and medulla interspersed with areas of pale tissue. The latter showed glomerular immaturity associated with a range of degenerative processes involving the glomeruli and tubules. The condition bore many similarities to that of renal cortical dysplasia in other species.