JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

December 2023

U-M13 (NP)

 

Signalment (JPC #2370242): A nine-year-old Basenji dog

 

HISTORY: This dog had polyuria, polydipsia, and glycosuria for two years and was euthanized. A littermate with a similar history of chronic polyuria, polydipsia, and glycosuria was euthanized one week prior. Both dogs had normal blood glucose levels. 

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Affecting approximately 80% of the renal medulla, there is a regionally extensive area of retention of cellular architecture with loss of different (coagulative necrosis). Multifocally remaining tubules are often mildly ectatic and sometimes contain eosinophilic proteinaceous material (proteinosis) or cellular debris. Tubular epithelium multifocally displays one or more of the following changes: attenuation, karyomegaly with nuclei up to 22µm in diameter finely stippled chromatin with abundant granular cytoplasm, are swollen with vacuolated cytoplasm (degeneration), are shrunken and with a pyknotic or absent nucleus (necrotic), or are lost. Proximal tubular epithelial cells often contain acidophilic brick-shaped intranuclear inclusions (ACIN inclusions). Multifocally within the interstitium, there are low to moderate numbers of lymphocytes and plasma cells. Rarely glomeruli display one of the following changes: mild segmental expansion of the basement membranes by eosinophilic material, mild hyperplasia of visceral epithelium, or mild dilation of Bowman’s capsule with atrophy of the glomerular tuft (glomerulocystic change). The renal capsule is mildly thickened by fibrous connective tissue.

 

MORPHOLOGIC DIAGNOSIS: Kidney: Necrosis, medullary, coagulative, focally extensive, with tubular degeneration and tubular epithelial karyomegaly, Basenji, canine.

Kidney: Nephritis, interstitial, lymphoplasmacytic, chronic, multifocal, mild. 

 

ETIOLOGIC DIAGNOSIS: Hereditary tubular nephropathy

 

CONDITION: Fanconi-like Syndrome 

 

GENERAL DISCUSSION: 

• Fanconi-like Syndrome: An adult onset, slowly progressive, proximal renal tubular disorder, resulting in impaired renal tubular reabsorption of amino acids, glucose, and electrolytes; similar to Fanconi syndrome in humans
• Hereditary in the Basenji (recessive lethal gene); also described in Irish wolfhounds
• It can be produced experimentally in dogs and rats with maleic acid
• Acquired Fanconi syndrome has been reported in dogs in association with renal toxins (gentamicin, chicken jerky treats, lead, etc.). nephrotoxicity, ethylene glycol nephrotoxicity, primary hypoparathyroidism, and copper storage hepatopathy 

 

PATHOGENESIS:

 

TYPICAL CLINICAL FINDINGS:

• Polyuria (results from the glucosuria and natriuresis), polydipsia, hyposthenuria
• Dehydration and acidosis (causes renal papillary necrosis)
• Paradoxic glucosuria (glucosuria with normoglycemia), hyperphosphaturia, proteinuria; aminoaciduria (generalized or limited to cystinuria)
• Hyperphosphatemia
• Renal tubular acidosis (proximal tubular, type II) due to failure to resorb filtered bicarbonate 

 

TYPICAL GROSS FINDINGS:

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Initially minimal with irregularly sized tubular epithelial cells (marked hypertrophy & karyomegaly) in the convoluted tubules and loops of Henle
• Nonspecific interstitial fibrosis and tubular atrophy

 

DIFFERENTIAL DIAGNOSIS:

• Primary tubular transport defects in domestic animals:  

• Hyperuricosuria in Dalmatian dogs
• Primary renal glucosuria in Norwegian Elkhounds, Scottish Terriers

• Secondary causes of tubular dysfunction: Diabetes mellitus, acute enterotoxemia, and heavy metal toxicity 
• Papillary necrosis may be due to urinary obstruction, pyelonephritis, or nonsteroidal anti-inflammatory drugs 

 

COMPARATIVE PATHOLOGY:

• Humans: Acquired Fanconi Syndrome has been observed with amyloidosis, multiple myeloma, and administration of some drugs
• Fanconi-like syndrome has been reported in quarter horses (cause unknown); idiopathic and possibly inherited Fanconi syndrome reported in a heifer
• Cats may have a transient acquired Fanconi syndrome in response to chlorambucil (chemotherapeutic) treatment 
• Karyomegaly of the tubular epithelium may occur secondary to Pyrrolizidine alkaloid toxicity 
• Most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi syndrome)

 

Other breed-related diseases of Basenjis:

• Familial hemolytic anemia due to pyruvate kinase deficiency 
• Chronic hypertrophic gastritis
• Immunoproliferative enteritis with high circulating levels of IgA

 

REFERENCES:

1. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. 6th ed. Vol 2. Philadelphia, PA: Elsevier Saunders;2016:428-429.
2. Stockham SL, Scott MA. Calcium, Phosphorus, Magnesium, and Their Regulatory Hormones. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:620.
3. Stockham SL, Scott MA. Urinary system. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:463.
4. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:753-754.

 

 

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