JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

November 2023

U-B01

 

SIGNALMENT: (JPC #2237297) Tissue from a dog.

 

HISTORY: None provided.

 

CBC               Range            Chemistry                 Range            Urinalysis

WBC 23.1      (5-14.1)          Phos 12.7                  (2.9-5.3)         S.G.                1.020

Segs 84%                              BUN 159                    (8-28)              pH                   6.5 

Lymphs 6 %                          AST    186                 (13-15)           Protein           952 mg/dl

Monos 7%                             Creatinine 6.7           (0.5-1.7)         Creatinine     73 mg/dl

Bands 1%                              Cholesterol 340        (135-278)       Blood              3+

Eos 2%                                  T.P.     5.1                   (5.4-7.5)         

                                                Alb      2.1                   (2.3-3.1)

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Diffusely, glomeruli vary in size and are either expanded, measuring up to 400 µm in diameter, or are shrunken (atrophied) with mild expansion of the uriniferous space (glomerulocystic atrophy). Multifocally, glomeruli exhibit one or more of the following changes: 1) mesangial hypercellularity with the presence of few neutrophils and scattered eosinophilic and karyorrhectic cellular debris (necrosis), 2) thickening of glomerular capillary loops up to three times normal due to endocapillary hypercellularity, 3) expansion of glomerular mesangium by variable amounts of eosinophilic fibrillar material, and/or 4) thickening of glomerular basement membranes. Other glomerular changes include: hypertrophy and hyperplasia of parietal and visceral epithelium of Bowman’s capsule, adhesions between parietal and visceral epithelium of Bowman’s capsule (synechiae), expansion of the uriniferous space by hypereosinophilic homogenous material (proteinaceous fluid) and/or fibrin (glomerular crescent), and periglomerular fibrosis and mineralization. Tubules are multifocally ectatic, up to 150 µm in diameter, and often exhibit one or more of the following changes: 1) expansion of the lumen by eosinophilic proteinaceous fluid (tubular proteinosis), 2) attenuation of epithelium, 3) necrosis characterized by shrunken hypereosinophilic epithelial cells with pyknotic nuclei, 4) swollen epithelial cells with vacuolated cytoplasm (degeneration), 5) regeneration characterized by epithelium that is piled up with increased cytoplasmic basophilia, or 5) filling of tubule lumina by sloughed epithelial cells admixed with cellular debris (granular cast). Multifocally and extensively, tubule epithelial cell cytoplasm contains brown globular pigment (hemosiderin or lipofuscin). Scattered throughout the cortical interstitium, there are multifocal aggregates of lymphocytes and plasma cells that often surround glomeruli and vessels.  

 

MORPHOLOGIC DIAGNOSIS: Kidney: Glomerulonephritis with glomerular hypercellularity and glomerular basement membrane thickening, chronic, global, diffuse, moderate, with tubular degeneration, necrosis, and regeneration, and lymphoplasmacytic interstitial nephritis, breed unspecified, canine. 

 

ETIOLOGIC DIAGNOSIS: Borrelial glomerulonephritis

 

CAUSE: Borrelia burgdorferi

 

CONDITION: Lyme disease, Lyme borreliosis, Lyme nephritis

 

GENERAL DISCUSSION:  

• B. burgdorferi is a gram-negative, pathogenic spirochete that is transmitted by hard ticks of the Ixodes spp. genus
• May cause a multisystemic disease (Lyme disease); infection is more common than disease
• Arthritis is a common presentation in animals and humans; less commonly dogs may develop myocarditis and nephritis; cattle experience abortion; horses develop myocarditis and encephalitis
• May cause rapidly progressive membranoproliferative glomerulonephritis (MPGN); 

• The diagnosis of MPGN requires identification of immune complex deposition leading to the remodeling of capillary loops and proliferation of cells (endocapillary and mesangial), for this reason special stains or electron microscopy is necessary to make this diagnosis

• Labrador and Golden Retrievers are over-represented in the incidence of renal disease

 

LIFE CYCLE:  

• Ixodes ticks have a 2-year life cycle: Eggs are laid in the spring > develop into larvae which feed on small mammals/reptiles in summer > then adults feed on deer/large mammals in fall and maintain the disease through overwintering of infected nymphs; birds disperse infected ticks to new areas
• Borrelia burgdorferi ingested by an Ixodes tick during a blood meal > localizes in tick gut via outer surface protein A (Osp A) > when the tick attaches to a new host and begins a blood meal, there is an increase in temperature within the tick which causes a change in expression of outer surface proteins from Osp A to Osp C > Osp C allows the spirochete to localize to the tick salivary glands within 48 hours of tick attachment > the spirochete then enters the host through the tick’s mouthparts

 

PATHOGENESIS:  

• Exact mechanism of renal damage is unclear 
• Disease thought to be driven by immune complexes containing a variety of antigens including OspA, OspB, and/or flagellin
• B. burgdorferi is a persistent pathogen that can evade immune clearance; organisms are NOT frequently found in the kidney; clinical illness results from the host's inflammatory response

 

TYPICAL CLINICAL FINDINGS:  

• Most common signs in dogs: anorexia, lethargy, lameness with fever and lymphadenopathy
• Occasionally, signs of acute, progressive renal failure - uremia, azotemia, proteinuria, peripheral edema, body cavity effusions
• Arthritis is often intermittent and involves one or more joints

 

TYPICAL GROSS FINDINGS:  

• Typically light tan (occasionally red-brown ‘golden kidney’) renal cortex, multifocal red pinpoint foci, diffuse bulging of the medulla on section
• Limited gross changes seen in arthritis, although joint effusion is reported

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Kidney: Classic triad of renal lesions:

• Diffuse membranoproliferative glomerulonephritis with periglomerular fibrosis and glomerular synechiae to Bowman's capsule; variable crescent formation (fibrin, inflammatory cells within uriniferous space)
• Multifocal tubular necrosis and regeneration, cortical tubular dilation, and luminal protein casts
• Lymphoplasmacytic interstitial nephritis

• Joints: In affected joints, findings are primarily microscopic synovitis with lymphocytes and plasma cells within the subintimal tissue of the synovia

 

ULTRASTRUCTURAL FINDINGS:  

• Multifocal electron-dense subendothelial deposits along the glomerular basement membrane (GBM) with visceral epithelial cell foot process fusion
• Expansion, folding, and splitting of the GBM
• Increase in mesangial matrix
• Swelling and vacuolization of parietal cell cytoplasm

 

ADDITIONAL DIAGNOSTIC TESTS:

• Validated IHC for antigens is not available
• Lyme borreliosis serology against outer surface proteins (Osp) C and F or recombinant protein C6
• Silver or Romanowsky-type stains (Giemsa, Wright’s) – organisms are rarely present in the kidney
• Antigenically distinct antibodies to DbpA or DbpB are produced during canine infection; the response is not confounded by vaccination with a Lyme disease bacterin
• Genomic hybrid capture assay

 

DIFFERENTIAL DIAGNOSIS:  

• Membranoproliferative glomerulonephritis and tubulointerstitial disease in dogs:

• Leishmania spp.
• Canine adenovirus-1

• Other causes of immune-complex glomerulonephritis in dogs:

• Dirofilaria immitis

 

COMPARATIVE PATHOLOGY:  

Borrelia burgdorferi in other species:

• Non-human primates – Meningitis
• Neuroborreliosis reported in a horse with common variable immunodeficiency (Pecoraro, J Vet Diagn Invest. 2019)
• Single report of disease in a red fox
• Horses in Ontario, Canada

Other Borellia sp.:

• Fowl: B. anserina causes avian borreliosis/fowl spirochetosis of chickens, turkeys, geese, ducks, and other avian species; spread by Argas persicus
  • Affected birds are depressed, cyanotic, thirsty, and often have a diarrhea that includes excessive white urates.

 

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: 410-412.
2. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals  6th ed. vol 1. St. Louis, MO: Elsevier; 2016: 152.
3. Divers TJ, Mongodin EF, Miller CB, Belgrave RL, Gardner RB, Fraser CM, Schutzer SE. Genomic hybrid capture assay to detect Borrelia burgdorferi: an application to diagnose neuroborreliosis in horses. J Vet Diagn Invest. 2022;34(5):909-912.
4. Fulton RM, Boulianne M. Bacterial Diseases. In: Boulianne M ed. Avian Disease Manual. 8^th ed. Madison, WI: Omnipress; 2019: 108, 129, 229.
5. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 244.
6. Neely M, Arroyo L, Jardine C, Clow K, Moore A, Hazlett M, Weese JS. Evaluation of 2 ELISAs to determine Borrelia burgdorferi seropositivity in horses over a 12-month period. J Vet Diagn Invest. 2021;33(4):736-739.
7. Oldenburg DG, Jobe DA, Lovrich SD, LaFleur RL, White DW, Dant JC, Callister SM. Detection of antibodies to decorin-binding protein A (DbpA) and DbpB after infection of dogs with Borrelia burgdorferi by tick challenge. J Vet Diagn Invest. 2020;32(3):481-485.
8. Olson, Erik J., Dykstra, Jaclyn A., Armstrong, Alexandra R., and Carlson, Cathy S.  Bones, Joints, Tendons, and Ligaments, In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1086.
9. Pecoraro HL, Felippe MJB, Miller AD, Divers TJ, Simpson KW, Guyer KM, Duhamel GE. Neuroborreliosis in a horse with common variable immunodeficiency. J Vet Diagn Invest. 2019;31(2):241-245.
10. Sula, Mee-Ja M., Lane, Laura V.  Urinary system, In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:751.

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