JPC SYSTEMIC PATHOLOGY
URINARY SYSTEM
January 2024
U-T13
Signalment (JPC #1218877): A pig
HISTORY: Free ranging pig developed trembling, weakness, incoordination, and coma.
HISTOPATHOLOGIC DESCRIPTION: Kidney: Within the cortex and medulla, 80-85% of the renal tubules are mildly ectatic and exhibit one or more of the following changes: degeneration, characterized by swollen epithelial cells with vacuolated eosinophilic cytoplasm and hyperchromatic nuclei; necrosis, characterized by hypereosinophilic cytoplasm, and karyorrhectic or faded nuclei; or regeneration, characterized by basophilic cytoplasm, vesiculate nuclei, and rare mitoses. Tubular and ductal lumina contain varying amounts of eosinophilic proteinaceous material (proteinosis) and occasional aggregates of sloughed epithelial cells and neutrophils (cellular casts). Multifocally, Bowman’s space is moderately dilated and contains brightly eosinophilic homogenous proteinaceous material. There is edema in the peripelvic connective tissue characterized by numerous markedly dilated lymphatics that contain moderate amounts of beaded fibrillar eosinophilic material (fibrin) and few lymphocytes, plasma cells and erythrocytes. Focally within the renal papilla, the urothelium is attenuated, there is peri-pelvic fibrosis, and the subjacent parenchyma is compressed into a 5 mm band of tissue with dilated renal tubules (hydronephrosis). Multifocally, the capsule is depressed overlying wide radiating bands of fibrous connective tissue that extend from the capsule to the pelvis. In these areas of fibrosis, there is tubular and glomerular loss, tubular atrophy, and glomerulosclerosis. Scattered throughout the interstitium there are moderate numbers of lymphocytes, fewer plasma cells and neutrophils, and rare eosinophils.
MORPHOLOGIC DIAGNOSIS: Kidney: Tubular degeneration, necrosis, and regeneration, multifocal, moderate, with diffuse peripelvic edema, granular and cellular casts, fibrosis, mild lymphoplasmacytic interstitial nephritis, and hydronephrosis, breed unspecified, porcine.
ETIOLOGIC DIAGNOSIS: Toxic nephropathy
CAUSE: Amaranthus retroflexus (redroot pigweed)
CONDITION: Perirenal edema disease
GENERAL DISCUSSION:
- Ingestion of Amaranthus retroflexus (redroot pigweed) causes acute tubular necrosis and perirenal edema in pigs, cattle, and uncommonly in horses
- A. retroflexus is a common weed throughout North America; disease occurs middle to late summer during peak weed growth
- Morbidity ranges from less than 5% to 50%; mortality is 75-80% in those showing clinical signs
- Lamb's quarter, black nightshade, buffalo burr, and Jimson weed are also suspected in causing perirenal edema
PATHOGENESIS:
- Perirenal edema: Epithelial necrosis > tubular backleak of ultrafiltrate > lymphatic drainage and leakage into perirenal connective tissue
- Acute tubular necrosis: Nephrotoxic principle is unknown; phenolic compounds have been identified in Amaranthus leaves; in acorn (oak) poisoning (Quercus spp.) in ruminants, similar compounds, gallotannin, are hydrolyzed to toxic metabolites (e.g. tannic acid) that bind and damage endothelial cells
- Death is probably due to hyperkalemic heart failure: Oliguric or anuric acute renal failure > failure to secrete H+ or reabsorb HCO3- from kidneys > elevation of mineral acids (NH4Cl, HCl) and titrational metabolic acidosis > translocation of K and H ions (H goes out, K goes in) > hyperkalemia > changes electrical potential of excitable cells (conduction cells > myocardial cells) > sinoventricular rhythm, ventricular fibrillation or standstill in the heart
- The plant contains oxalates and can accumulate nitrates; however, lesions associated with these toxins are not typically seen in pigs
TYPICAL CLINICAL FINDINGS:
- Clinical signs begin 5-10 days after ingestion
- Weakness, trembling, and ataxia
- Knuckling of pastern joints, hind limb paralysis, sternal recumbency
- Coma/death usually within 48 hours of initial signs due to hyperkalemic heart failure
- Clinical pathology: Elevated serum BUN, creatinine, CK, and potassium; proteinuria
TYPICAL GROSS FINDINGS:
- Marked perirenal edema which may be clear to serosanguineous
- Kidneys are usually normal size and pale
- Ascites; hydrothorax; edema of mesenteries, ventral abdominal wall, and perirectal tissues
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Hydropic degeneration and coagulative necrosis of proximal and distal tubules
- Tubular ectasia with protein and granular casts (distal tubules, collecting ducts)
- Dilatation of Bowman's space; shrunken glomeruli
- Chronic lesion: Cortical interstitial fibrosis; ectatic tubules with attenuated epithelium
DIFFERENTIAL DIAGNOSIS:
- Edema disease (Escherichia coli): Shiga-like toxin-II variant causes generalized endothelial injury leading to palpebral, mesenteric (spiral colon), gastric, and gallbladder edema; there may also be cerebral edema and malacia
- Ochratoxin A (mycotoxin): Tubular degeneration and necrosis; may produce perirenal edema
- Oak toxicity: May produce nephrotoxic tubule necrosis and perirenal edema in cattle
- Heavy metal nephrosis: Mercury, lead, arsenic; acute tubular necrosis due to tubular membrane or mitochondrial damage
- Stephanurus dentatus: Kidney worm of pigs; perirenal and pelvic cysts
- Piquillin toxicity causes axonal degeneration of the white matter in the ventral funiculi of the lumbosacral spinal cord leading to ataxia
COMPARATIVE PATHOLOGY:
Examples of nephrotoxins in various species:
- Horse: Red maple leaf (not directly nephrotoxic); monensin; aminoglycosides
- Ox: Oxalates toxicity (Halogeton sp., Rumex sp., Sarcobatus sp.); oak (Quercus sp.); monensin; plants with vitamin D-like toxicity (Cestrum diurnum)
- Sheep: Oxalate toxicity
- Poultry: Monensin
- Rodents: Chloroform
- Dog: Ethylene glycol; NSAIDs; Tibetan spaniels with inherited hyperoxaluria; vitamin D nephropathy
- Cat: Ethylene glycol; vitamin D nephropathy; Easter lilies
- Pigs: Pigweed (Amaranthus retroflexus); Ochratoxin A (mycotoxin)
REFERENCES:
- Carson TL. Toxic minerals, chemicals, plants, and gases. In: Straw BE, Zimmerman JJ, D'Allaire S, Taylor DJ, eds. Diseases of Swine. 9th ed. Ames, IA: Iowa State University Press; 2006:977-978.
- 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; 2016:386, 427.
- Hovda LR. Disorders caused by toxicants. In: Smith BP, ed. Large Animal Internal Medicine. 5th ed. St. Louis, MO: Mosby Elsevier; 2015:1594.
- Sebastian MM. Role of pathology in diagnosis. In: Gupta RC, ed. Veterinary Toxicology. New York, NY: Elsevier Inc; 2007:171, 1125-1126.
- Sula, MM, Lane, LV. The urinary system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby/Elsevier; 2022:749.