JPC SYSTEMIC PATHOLOGY
URINARY SYSTEM
January 2018
U-T01 (NP)

Signalment (AFIP #1801670): Sprague-Dawley rat

HISTORY: Sprague-Dawley rat kidney removed two days after a single intraperitoneal injection of 75 ug/kg body weight of gold sodium thiomalate.

HISTOPATHOLOGIC DESCRIPTION:  Kidney:  Multifocally, the epithelium lining of up to 60% of cortical tubules, and fewer medullary tubules, is lost with replacement by eosinophilic, granular necrotic debris or undergoes one or more of the following changes: loss of cellular detail with hypereosinophilic cytoplasm, pyknosis, karyorrhexis, and karyolysis (necrosis); swollen, vacuolated cytoplasm with faded nuclei (degeneration); or amphophilic cytoplasm and occasional mitotic figures (regeneration).   Affected tubules and collecting ducts are often ectatic, and contain intraluminal eosinophilic, fibrillar to homogenous, proteinaceous fluid, which is often admixed with sloughed tubular epithelial cells and necrotic debris (granular casts).  Scattered throughout the interstitium are low numbers of neutrophils and lymphocytes.  Multifocally, the renal capsule is undulant, with depressions overlying aggregates of collapsed, necrotic tubules (stromal collapse).

MORPHOLOGIC DIAGNOSIS:  Kidney, tubules:  Necrosis, acute, multifocal, with degeneration and regeneration, Sprague-Dawley, rodent.

ETIOLOGIC DIAGNOSIS:  Renal chrysotoxicosis

CAUSE:  Gold sodium thiomalate

GENERAL DISCUSSION:

PATHOGENESIS:

  1. Direct toxicity to renal tubular epithelium: gold salts have high affinity for mitochondria of proximal convoluted tubule epithelium
  2. Immune-complex glomerulonephritis - two possible mechanisms:
    1. Gold acts as a hapten > formation antibodies against gold-protein complexes > subepithelial deposition in glomeruli
    2. Antibodies formed against damaged tubular mitochondria > antigen-antibody complexes deposited in glomeruli

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

DIFFERENTIAL DIAGNOSIS: Other nephrotoxins:

COMPARATIVE PATHOLOGY:  Examples of nephrotoxins in various species:

REFERENCES:

  1. Bennett D. Immune-mediated and infectious arthritis. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed. Vol. 1, St. Louis, MO: Elsevier Saunders; 2005:749.
  2. Breshears MA, Confer AW. The urinary system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO:  Elsevier; 2017:654-657.
  3. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed., Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 2. 6th ed. St. Louis, MO: Elsevier; 2016:422-428.
  4. Goyer RA, Clarkson TW. Toxic effects of metals. In: Klaassen CD, ed. Casarett and Doull’s Toxicology: The Basic Science of Poisons, 6th ed., New York, NY: McGraw-Hill; 2001:851.
  5. Sebastian MM, Baskin SI, Czerwinski SE. Renal toxicity. In: Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. San Diego, CA: Academic Press; 2007:163-176.
  6. Wexler P. Encyclopedia of Toxicology. Vol. 2. San Diego, CA: Academic Press; 1998:61.


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