Multicystic dysplastic kidney disease in a dog

Abstract

A 1-year-old female mongrel dog was evaluated for anorexia and vomiting of 4 days duration. Abdominal ultrasonographic findings revealed small kidneys with multiple anechoic cysts. The dog was euthanized due to poor prognosis. A full necropsy was performed, and the histopathologic findings were consistent with multicystic dysplastic kidney disease.

A 1-year-old, 2.5-kg, female mongrel dog was admitted to the Gyeongsang National University Veterinary Teaching Hospital with a presenting complaint of anorexia and vomiting for the previous 4 d. Vaccinations were up-to-date and there was no history of drug or toxicant ingestion. The owner reported that the dog was weaker and smaller than its littermates. The dog had been polydipsic and polyuric and had vomited intermittently since birth.

Case description

Physical examination revealed severe dehydration (8% to 10%), pale mucous membranes, prolonged capillary refill time, and halitosis. The dog was emaciated and the abdomen was tense on palpation.

A complete blood (cell) count revealed leukopenia [5400 cells/μL; reference range (RR): 6000 to 17 000 cells/μL], and moderate normocytic, normochromic, non-regenerative anemia [hematocrit (Hct), 27.5%; RR: 35% to 55%]. A biochemical profile revealed high concentrations of BUN (> 200 71.4 mmol/L; RR: 2.9 to 11.1 mmol/L) and creatinine (892 μmol/L; RR: 70.7 to 141.4 μmol/L), mild hyperglycemia (7.2 mmol/L; RR: 3.9 to 6.5 mmol/L), hypercalcemia (3.6 mmol/L; RR: 1.9 to 2.8 mmol/L), and hyperphosphatemia (2.13 mmol/L; RR: 0.68 to 2.03 mmol/L). Analysis of urine collected by cystocentesis revealed a specific gravity of 1.021, a pH of 7.0, proteinuria (1+), and glucosuria (1+). No significant abnormalities were detected on examination of the urine sediment and culture of the urine was not performed.

Abdominal radiographs revealed poor abdominal detail because of the dog’s emaciated body condition. Abdominal ultrasound revealed small kidneys with a loss of normal architecture and a poor corticomedullary distinction bilaterally. The right kidney had 3 large anechoic cysts and strong distal acoustic enhancement. Multiple sharply demarcated, thin-walled, round structures of various sizes containing anechoic fluid were detected in the right kidney; the cystic lesions in the left kidney were not as well-defined because of strong generalized acoustic shadowing caused by cortical hyperechogenecity (Figure 1). Treatment with a low protein diet (Prescription Diet Canine k/d, canned; Hill’s Pet Products, Topeka, USA), ranitidine HCl (Ranis; Skynewpham, Siheung, Korea), 2 mg/kg body weight (BW), BID, PO, and dried aluminum hydroxide gel (Amphojel; Ildong, Ansung, Korea), 50 mg/kg BW, BID, PO was initiated. Initial fluid therapy with 0.9% NaCl was given via a cephalic catheter at 20 mL/h with urine collection by a urinary catheter. The infusion rate was changed to 15 mL/h after 3 h of the initial fluid therapy. The dog was euthanized after 2 d of hospitalization because of a poor prognosis and worsening clinical signs.

Figure 1.

Sonographs of the left (A and B) and right (C and D) kidney. The kidneys are small, with loss of normal architecture due to cystic lesions and distal acoustic shadowing. Anechoic, multiple, sharply demarcated, thin-walled, round structures of various sizes were detected in the right kidney.

A full necropsy was performed. Both kidneys were pale tan and smaller than normal; each had an irregular capsular surface. The right kidney measured approximately 4 × 3 × 3 cm and had 5 large cysts ranging from 1 to 2 cm in diameter and numerous small cysts. The left kidney measured approximately 3 × 2 × 2 cm and had 5 to 6 large cysts approximately 0.5 to 1 cm in diameter. On the cut surface, the corticomedullary junction of both kidneys was obscure (Figure 2). Various sized cysts filled with clear fluid were present in subcapsular areas of the cortex. There were no similar lesions in any other visceral organs.

Figure 2.

Left (A) and right kidney (B). Both kidneys were a pale tan with an irregular capsular surface and were smaller than normal. On the cut surface, the corticomedullary junction of both kidneys was obscured. Various sized cysts were present in subcapsular areas.

Histopathological samples of kidney, lung, heart, liver, spleen, small intestine, stomach, pancreas, bladder, adrenal gland, trachea, uterus, and ovary were examined after staining with hematoxylin and eosin (H&E). Selected sections of kidney were stained with alcian blue (pH 2.5), Masson’s trichrome, periodic acid-Schiff (PAS), and von Kossa stains.

Microscopic examination of the subcapsular area of the kidneys revealed multiple, variable-sized cysts that were lined with single squamous epithelium (Figure 3A). Most cysts appeared empty, and some were surrounded by a fibrotic capsule. Some enlarged cysts in the cortex mimicked dilated Bowman’s capsules and were lined by a single cell layer of flattened epithelium. Multifocal dysplastic lesions were found throughout the cortex and medulla of both kidneys (Figure 3A). In dysplastic areas, immature glomeruli or tubules were distributed from the subcapsular area to the corticomedullary junction of both kidneys (Figure 3B), and associated with interstitial fibrosis and proliferative arterioles. In the medulla, irregularly shaped immature tubules, similar to metanephric ducts, were embedded in persistent mesenchyme (Figure 3C). These immature tubules were lined by pseudostratified, tall columnar epithelial cells. The persistent mesenchyme consisted of proliferated small spindle cells and stellate cells with myxomatous stroma, which was weakly stained with alcian blue but not with Masson’s trichrome. Adenomatoid proliferation of cuboidal epithelium was also present in the dilated collecting ducts of the medulla (Figure 3D).

Figure 3.

Microscopic appearance of the kidney. (A, right kidney) — There are large bands of fibrous connective tissue with irregular dilated cysts, and atrophic glomeruli within cystic Bowman’s capsules. Note the large cyst (*) in the subcapsular area, lined by flattened epithelium (insert, arrows). H&E, Bar = 200 μm. (B, right kidney) — Note the immature glomeruli (arrows), tubules (arrow head), and proliferative arteriole (open arrow) in the dysplastic area. H&E, Bar = 100 μm. (C, right kidney) — Primitive metanephric ducts lined by pseudostratified columnar epithelium (arrows) are embedded in loose mesenchyme. Note large cysts and mild inflammation. H&E, Bar = 200 μm. (D, left kidney) — Adenomatoid proliferation (arrows) of cuboidal epithelium in two dilated collecting ducts. H&E, Bar = 50 μm.

In both kidneys, varying degrees of degenerative and inflammatory lesions were noted. Interstitial fibrosis was present within the segmental cortical zones of immature nephrons. Cystic glomerular atrophy was also present in the areas of interstitial fibrosis. Severe mineralization positively stained with von Kossa and epithelial necrosis were present in most of the cortical renal tubules. Mild to moderate multifocal chronic pyelonephritis lesions containing lymphocytes, plasma cells, and macrophages were found in the renal pelvis and medulla (Figure 3C). Mild multifocal mineralization was found in the alveolar walls of the lung, and diffuse hemosiderosis was seen in the spleen; there were no other abnormalities.

Discussion

Multicystic dysplastic kidney disease, a type of renal dysplasia (1), is also referred to as renal dysgenesis, or multicystic kidney disease (2). Renal dysplasia has been described in several canine breeds, including Shih Tzu (3), border terrier (4), golden retriever (5,6), standard poodle (7), boxer (8), Finnish harrier (8), Rhodesian ridgeback (9), and Dutch kooiker (10). To the authors’ knowledge, this is the first reported case of chronic renal failure associated with renal dysplasia in a mongrel dog.

The causes of renal dysplasia in humans include genetic defects, lower urinary tract obstruction, and teratogens/drugs (11); the cause of renal dysplasia in dogs is unknown (4,8–10). In humans, the interaction between these causes leads to renal dysplasia and results in abnormal collecting duct development and branching, and the loss of potentially functional nephrons, as well as the formation of aberrant structures, such as cysts (11). In human renal dysplasia, cysts are considered coincidental findings. In canine renal dysplasia, cysts may be considered secondary degenerative changes, not a primary lesion of dysplasia (12). It was once thought that cyst formation was a consequence of tubular obstruction (13). Similarly, it was presumed that cystic changes in nephrons were attributed to progressive interstitial fibrosis in 1 study of dogs with renal dysplasia (12). Considering that interstitial fibrosis was present within the segmental cortical zones of immature nephrons and cystic glomerular atrophy was also present in the areas of interstitial fibrosis, as in this case, fibrosis seemed to cause formation of the cysts. Certain genes have been associated with the formation of renal cysts. In mice, deficiency of Bcl-2 contributes to cystic formation of the kidneys (13). In humans, mutation of TCF-1 and Pax-2 leads to cystic dysplastic kidneys (11). The possibility that genetic factors may have contributed to the disease or that the interstitial fibrosis secondary to chronic pyelonephritis may have led to the cyst formation cannot be ruled out.

The clinical signs in this case were those expected in dogs with advanced renal failure and included vomiting, anorexia, polyuria, polydipsia, and weight loss. Two clinical types of the renal dysplasia have been reported in Shih Tzu dogs (14). A severe type of renal dysplasia was seen in young dogs presenting with only a short history of clinical signs and with laboratory tests that reveal severe abnormalities suggesting renal disease. These dogs usually died within a few days or were euthanized (14). As indicated by a short history of clinical signs (4 days), severe hematological abnormalities, and poor prognosis in this case, it is considered to be a severe type of renal dysplasia.

The laboratory findings were those expected in dogs with advanced renal failure: azotemia, low urine specific gravity, hyperphosphatemia, and nonregenerative anemia. Usually hypocalcemia is observed more frequently in dogs with chronic renal failure (15), but hypercalcemia is present in young dogs with chronic renal failure (15,16). Although a cause of hypercalcemia was not identified, in our opinion hypercalcemia was associated with the young age. As for the hyperphosphatemia, increased plasma phosphate probably bonded with free ionized calcium, producing soft tissue calcification and reducing the ionized calcium concentration. Such a relationship between calcium and phosphate has been reported previously (17). Mineralization of the basement membrane of the Bowman’s capsules and renal tubules is frequently observed in dysplastic kidneys in dogs (3,10,12). Moderate to severe mineralization in renal tubules and alveolar walls in this case may be related to hypercalcemia.

The ultrasonographic features of renal dysplasia in dogs are poorly documented (5,6,8,9,18). Small, irregular hyperechoic kidneys with a poor corticomedullary distinction are described (5,6,9,18). In this case, the level of renal medullar echogenicity and the degree of abnormality could not be determined because of cystic lesions and the distal acoustic shadowing. The latter might have been caused by renal mineralization, which was confirmed histopathologically.

On ultrasonography, identification of renal cysts should distinguish multicystic dysplastic kidney from polycystic kidney disease. With polycystic disease, the kidneys are usually larger than normal and concurrent cystic lesions may be present in other organs such as the liver and pancreas (12,19,20). In contrast, multicystic dysplastic kidneys are usually smaller than normal, and cystic lesions are only found within the kidneys (12).

Although ultrasonography helps in the diagnosis of multicysic dysplastic kidney disease, definitive diagnosis comes from histological analysis (5). Histopathologic findings in this dog were consistent with the criteria for renal dysplasia, and therefore multicystic dysplastic kidney disease was diagnosed. Five primary features of dysplasia in dogs are fetal/immature glomeruli and/or tubules (asynchronous differentiation of nephrons), persistent mesenchyma, persistent metanephric ducts, atypical or adenomatoid tubular epithelium which lining the collecting ducts, and dysontogenic metaplasia (5,8–10,12,21). Associated with and often obscuring the primary lesions of renal dysplasia, various degrees of compensatory, degenerative, and inflammatory lesions are observed in the affected kidneys (12). In both kidneys in the present case, there were immature glomeruli, primitive mesenchyme and metanephric ducts, and adenomatoid proliferation of tubular epithelium in the dilated collecting ducts.

Gross lesions of renal dysplasia are similar and often indistinguishable from end stage lesions in old dogs (10,12). Reduced numbers of normal nephrons are responsible for increased intrarenal vascular resistance, which eventually leads to chronic renal disease and hypertension (11,22). Renal dysplasia has been reported as a cause of chronic renal failure in juveniles and young adult dogs (8–10,23). It has been suggested that dysplastic kidneys may be susceptible to pyelonephritis (12,23). Renal tubular degeneration and dystrophic mineralization can also elicit inflammatory response in some cases of dysplastic kidneys (12). Although many secondary lesions are found in renal dysplasia, adenomatoid epithelium within tubules is a unique feature of renal dysplasia. The chronic pyelonephritis observed in this case is likely secondary, as adenomatoid proliferation of cuboidal epithelium was identified in the dilated collecting ducts of the medulla.

Treatment of dogs with renal dysplasia is usually supportive. One report suggested that clinical signs improved after initiation of supportive therapy and protein restricted diets in a dog with renal dysplasia (5). However, the prognosis of renal dysplasia in dogs is generally poor; most patients either die within a few days of supportive therapy or euthanasia is performed (3,6,9). Although similar treatment was performed as indicated in a previous report (5), there was no clinical improvement. In order to correct dehydration, the infusion of initial fluid therapy was done at a rapid rate. Erythropoietin (EPO) was scheduled to be prescribed as progress was carefully observed. However, due to the poor prognosis, euthanasia was performed without the EPO treatment. We did not include antibiotics as part of our treatment because pyelonephritis was not diagnosed. The treatment would have yielded a better prognosis, in our opinion, if pyelocentesis or fine-needle aspiration of the renal cysts was performed to evaluate the presence of urinary tract infection. CVJ