JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

November 2023

U-M03 

 

SIGNALMENT (JPC # 1574396, U-M03a): Cat, breed not specified

 

HISTORY: Incidental finding in a cat

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Multifocally, approximately 60% of the cortex and medulla are expanded by numerous 1 to 8 mm in diameter cysts that are lined by a single layer or multiple layers of attenuated or cuboidal epithelial cells, and distended by clear space or filled with eosinophilic homogenous material (proteinaceous fluid), which occasionally contains acicular cholesterol clefts and rare macrophages. Multifocally within the adjacent parenchyma, cysts compress adjacent ducts and tubules with mild to moderate atrophy and loss. Diffusely, remaining cortical tubules are mildly ectatic and often lined by atrophic or degenerate epithelium. Multifocally, dilated medullary tubules are lined by attenuated or hypertrophied epithelium and often surround a lumen with eosinophilic proteinaceous material, hemorrhage, and/or rare lymphocytes. Multifocally, the interstitium is mildly expanded by fibrous connective tissue admixed with variable numbers of lymphocytes and plasma cells, and rare deposits of basophilic, granular mineral. Diffusely, the capsular surface is irregular.  

 

MORPHOLOGIC DIAGNOSIS: Kidney: Cysts, multiple, with chronic, moderate lymphoplasmacytic interstitial nephritis and tubular atrophy, loss, and ectasia, breed not specified, feline.

 

SIGNALMENT (AFIP # U-M03b): Goldfish

 

HISTORY: The goldfish appeared less agile than other fish in the school and had difficulty with buoyancy. 

 

HISTOPATHOLOGIC DESCRIPTION: Kidney, metanephros: Multifocally the renal parenchyma is markedly expanded by multiple 0.5 to 4 mm diameter cysts that are lined by attenuated epithelial cells and distended by clear space. Cysts compress the adjacent renal parenchyma with mild atrophy and loss of ducts and tubules. Multifocally, remaining tubules are moderately ectatic and occasionally contain granular to cellular debris.  

 

MORPHOLOGIC DIAGNOSIS: Kidney, metanephros: Cysts, multiple, with moderate tubular ectasia and atrophy, goldfish, piscine.

 

CONDITION: Polycystic kidney disease (PKD)

 

GENERAL DISCUSSION:  

• Polycystic kidney disease, known inheritance: 
  1. Autosomal dominant PKD (ADPKD)
     • Bull terriers and Persian cats; both have a mutation in PKD1
     • Pigs and sheep (PBVD)
  2. Autosomal recessive PKD (ARPKD) 
     • West Highland white terriers, Cairn terriers, and Perendale sheep (PBVD also pigs and lambs); may be accompanied by hepatic biliary cysts 
• Congenital PKD, of unknown inheritance, occurs in piglets, lambs, calves, goat kids, puppies, kittens, and foals; human diagnosis is multicystic dysplasia 
• Highly penetrant; high variability in severity of expression among animal species and individuals within the species 
• In glomerulocystic disease, cysts only develop in Bowman's space (occasionally seen in stillborn foals and Collie dogs)

 

PATHOGENESIS:  

• Polycystic kidney disease occurs in 2 major forms:
• Autosomal dominant inheritance (similar to the adult form in humans)  
  • Mutation(s) of the PKD1 and/or PKD2 genes 
  • PKD1 and PKD2 code polycystin-1 and polycystin-2, respectively; these are transmembrane proteins that are important in cell-to-cell and cell-to-matrix interactions and calcium channeling; also associated with renal tubular development, signal transduction, control of cell cycle, and migration 
  • Both polycystin-1 and polycystin-2 are localized to the primary cilium of tubular epithelial cells; the cilium functions as a mechanosensor and regulates calcium signals
  • Proposed pathogenesis: Polycystin-1 and polycystin-2 mutations modify cilia function, cell proliferation, and migration à tubular epithelial proliferation and increased fluid secretion AND loss of polycystin-1 à alterations of critical pathways controlling normal tubulogenesis
  • Cysts are progressive, bilateral, and of proximal or distal tubule origin; may lead to chronic tubulointerstitial nephritis and renal failure 
  • PKD1 defects in Persians is also associated with hepatic cysts and/or hepatic fibrosis, and pancreatic cysts 
  • PKD1 defects in Bull Terriers may also cause abnormal glioblastomas
• Autosomal recessive inheritance (similar to the childhood form in humans)

• Pathogenesis unknown; in humans, mutation of the PKHD-1 gene encoding fibrocystin (a receptor protein located to the primary cilium)
• In West Highland white terriers, PKD may be accompanied by hepatic biliary cysts

• Other mechanisms that can lead to formation of renal cysts (not considered PKD):
  • Obstructive lesions which include acquired cysts of chronic renal disease, dysplastic cysts and glomerulocystic disease
  • Changes in the tubule basement membrane that result in dilation and formation of cystic structures; proximal tubule can also detach resulting in formation of atubular glomeruli
  • Disordered growth of tubular epithelium
  • Chemicals and drugs including corticosteroids can induce formation

 

TYPICAL CLINICAL FINDINGS:  

• Stillbirths or early death in severely affected animals
• ARPKD lambs die in utero or shortly after birth 
• Animals that survive can have enlarging cysts that impair renal function à renal failure

 

TYPICAL GROSS FINDINGS:  

• Kidneys are large, pale, smooth and shiny; contain numerous 1-5 mm diameter cysts with clear/opaque walls and contain watery liquid material
• Bile duct cysts range from barely visible to up to 3 cm in diameter; biliary system is distended; hepatic discoloration from bile
• “Swiss cheese” appearance on cut surface

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Numerous cysts that involve any part of the nephron, with compression of the renal parenchyma of surrounding connective tissue; PBVD states that cysts arise within the cortical tubules and enlarge to compress adjacent parenchyma leading to atrophy
• Cysts are oval, spherical or fusiform, lined by attenuated or cuboidal epithelium and can be divided by thin trabeculae
• May be accompanied by tubulointerstitial nephritis

 

DIFFERENTIAL DIAGNOSIS:  

• Simple renal cysts – one to many in cattle and pigs
• Hydronephrosis - dilated renal pelvis 
• Acquired renal cysts that are the result of interstitial fibrosis and usually occur in kidneys with extensive scarring
• Obstructive lesions
• Perinephric pseudocysts in the space between renal capsule and renal reflection of the peritoneum (not lined by epithelium)
• Experimental induction of renal cysts by chemical agents: long-acting corticosteroids, diphenylamine, polychlorinated biphenyls, 5,6,7,8-tetrahydrocarbazole-3-acetic acid, alloxan, diphenylthiazole, and norihydroguaiaretic acid
• Differential diagnoses for abdominal swelling in fish: Myxozoan infection (Hoferellus carassii – kidney bloater disease); bacterial infection (bacterial kidney disease of salmonids); abdominal neoplasia such as nephroblastoma, renal adenocarcinoma; osmoregulatory failure 

 

COMPARATIVE PATHOLOGY:  

• BALB/c mice: Prone to renal congenital cysts  
• New Zealand White rabbits: PKD reported; cysts found in cortex, less than 2 mm +/- visible grossly; microscopic dilation of Bowman’s space; thickening and splitting of the basement membrane with interstitial expansion; suspected genetic basis
• Inbred IIIvo rabbits: single to several hundred small cortical cysts; arise after 1 month of age; autosomal recessive 
• Nonhuman primates: PKD may manifest during infancy or adult life; inherited; single or multiple defects; kidneys are enlarged due to failure of fusion of the upper renal tubules and the collecting tubules àdistortion and engorgement of the proximal segment 

• Two reports of infantile PKD
• Most cases are the adult form and have ben reported in squirrel monkeys, pig-tailed macaques, titi monkeys, and baboons 

• Slow lorises: Progressive polycystic kidney disorder with high prevalence 
• Captive springbok: Neonatal polycystic kidney disease; up to 18% of live births in one captive population; consistent with ARPKD  
• Captive pygmy hippopotamus: Up to 35% prevalence of PKD; similar to ADPKD

• Microscopy: Previously described tubular cysts; bowman’s capsule are dilated and membranous glomerulopathy has been described; interstitial fibrosis; biliary cysts; cystic Bruner’s glands; other organs also affected

• Deer: PKD occurs regularly in Roe deer and has been reported in white-tailed deer
• Peccaries: PKD reported; assumed to be acquired not genetic
• Captive Pallas’ cats in North American zoos; diagnosed with PKD in adulthood; cysts confined to kidneys; genetic cause suspected 
• Reported in a captive aged racoon; single or multiple extensive renal cysts are occasionally diagnosed in dwarf mongoose
• Captive Brazilian agoutis: no clinical signs; potentially genetic; bilateral renal atrophy with a roughened granular cortical surface and multiple cysts 
• Polycystic disease is reported in goldfish

 

REFERENCES:  

1. Abee CR, Mansfield K, Tardif S, Morris T. Urogenital System. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2nd ed. San Diego, CA: Elsevier; 2012:297.
2. Bilgen N, Turkmen MB, Kul BC, et al. Prevalence of PKD1 gene mutation in cats in Turkey and pathogenesis of feline polycystic kidney disease. J Vet Diagn Invest. 2020;32(4):549-555.
3. Church ME, Terio KA, Keel MK. Procyonidae, Viverridae, Hyenidae, Herpestidae, Eupleridae, and Prionodontidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:308.
4. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:394-396.
5. Howerth EW, Nemeth NM, Ryser-Degiorgis MP. Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:152-153.
6. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae,Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:121.
7. Martinez MAJ, Gasper DJ, Mucino MCC, Terio KA. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:208.
8. Noga EJ. Problems 58 through 76: Diagnosis made by necropsy of the viscera and examination of wet mounts or histopathology of internal organs. Fish Disease: Diagnosis and Treatment. 2nd ed. Ames, IA: Wiley Blackwell; 2010:239.
9. Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:103, 319.
10. Schmidt R, Reavill DR, Phalen DN. Urinary System. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:130.
11. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:724-725.
12. Terio KA, McAloose D, Mitchell E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:266.

Click the slide to view.

---