JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

January 2024

U-T18

 

 

Signalment (AFIP # 2948647): One-year-old mixed breed dog.

 

HISTORY: The dog had clinical signs of gradual weight loss, vomiting, and anorexia. 

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Multifocally, cortical and medullary tubules are filled and expanded by 10-80 µm diameter, round, green-brown, birefringent crystals, occasionally arranged in concentric circles. Tubular lumina also multifocally contain: basophilic granular material (mineral), sloughed necrotic epithelial cells, necrotic debris and/or granular eosinophilic material (protein). Tubular epithelial cells multifocally exhibit the following changes: pale with swollen vacuolated cytoplasm (degeneration) or hypereosinophilic, shrunken angular cytoplasm with pyknotic nuclei (necrosis). There is loss of tubular architecture, tubulorrhexis and tubular basement membranes are multifocally lined or replaced by a basophilic smooth band of mineral.  The interstitium is multifocally, mildly to moderately expanded and replaced by fibrous connective tissue and edema. The renal capsule is thickened 2-3x normal by fibrous connective tissue and is mildly pitted/undulating.  

 

MORPHOLOGIC DIAGNOSIS: Kidney, tubules: Degeneration and necrosis, diffuse, moderate, with intratubular melamine/cyanuric acid crystals, interstitial fibrosis, and multifocal mineralization, mixed breed, canine.

 

CAUSE: Melamine/cyanuric acid toxicosis

 

ETIOLOGIC DIAGNOSIS: Toxic nephropathy  

 

GENERAL DISCUSSION: 

• In 2007 there was an outbreak of renal failure in dogs and cats associated with the ingestion of melamine and cyanuric acid adulterated pet food 
  1. Melamine and cyanuric acid are nitrogen-rich compounds that were added to artificially elevate dietary protein content

• Acute Tubular Injury (ATI), previously referred to as “nephrosis” or “acute tubular necrosis” (ATN), is generally due to nephrotoxins or ischemia and is an important cause of acute renal failure (ARF)
  1. Chemicals inducing crystal formation (such as calcium oxalate or melamine) are considered nephrotoxins
  2. Animals with ARF due to ATI are often oliguric or anuric and die within a few days without treatment

 

PATHOGENESIS:  

• Ingestion of melamine in combination with cyanuric acid -> insoluble crystal formation -> renal tubular epithelial damage (especially the distal nephron) -> renal failure
• Development of renal failure likely related to preexisting renal disease and urine pH

• Tubules and interstitium are intimately associated and damage to one affects the other; additionally, nephrotoxic ATI may lead to secondary ischemic injury (e.g., due to tubuloglomerular feedback)

 

TYPICAL CLINICAL FINDINGS:

• Melamine/cyanuric acid toxicosis: Inappetence, vomiting, polyuria, polydipsia, and lethargy; azotemia
• ARF secondary to ATI: Azotemia, hyperphosphatemia, hyperkalemia; proteinuria, isosthenuria, oliguria or anuria

 

TYPICAL GROSS FINDINGS:  

• Evidence of acute tubular necrosis (pale, swollen kidneys with the cut surface is pale and moist with bulging of the cortex) 
• +/- Yellow discoloration associated with crystalline deposits

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Melamine/cyanuric acid toxicosis: Prominent intratubular green to gold-brown circular birefringent crystals with radiating spokes in the more distal tubular portions of the nephron 
  1. Crystals may be dissolved and lost with prolonged formalin fixation (>6 mos)
  2. Scattered oxalate crystals may also be present and may be secondary to renal failure 
  3. General findings in ATI: Hyaline droplets in PCT cytoplasm, degeneration and necrosis of tubular epithelium, cellular and granular casts, tubular regeneration

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:

 

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. St. Louis, MO: Elsevier; 2016:421-424, 425, 427.
2. Cohen SM. Crystalluria and Chronic Kidney Disease. Toxicol Pathol. 2018;46(8):949-955. 
3. Ewing PJ, Meinkoth JH, Cowell RL, Tyler RD. The Kidneys. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:375, 378. 
4. Snyder L and Seelig D. Urinary System. In: Raskin RE, Meyer DJ, and Bowes KM. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:-399, 401. 
5. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:706, 711, 734-736.

 

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