Signalment:  

2.5-year-old female Bernese mountain dog, Canis familiarsA 2.5-year-old female Bernese mountain dog was referred to the Veterinary School of Nantes for a 3-month history of vomiting, weight loss, dysorexia and apathy. Physical examination revealed a marked amyotrophy and pale mucous membranes.

Gross Description:  

At necropsy, the dog had a poor condition score with pale and subicteric mucous membranes. Kidneys were diffusely pale, white-to-tan, with a marked generalized granular capsular surface. The cortex had numerous red-to-tan dots and had spongious aspect after formaldehyde fixation.

Other lesions included slight petechial hemorrhages of the stomach mucosa (confirmed by histology and associated with a laminar marked endothelial mineralization and necrosis on Alizarin red stain). Spleen was mildly firm, increased in size, and liver slightly and diffusely dark (HE and Perls stained slides: splenic and hepatic hemosiderosis and splenic macrophagous hyperplasia and extramedullary hematopoe+â-»sis). 10 mL of serous pericardial effusion was found.

Histopathologic Description:

Diffusely, glomerular tufts are enlarged with severe dilation of urinary chambers, increased tufts lobulation, thickening of the glomerular basement membrane, fibrotic changes including synechiae, capsular fibrosis and obsolescent glomeruli. Multifocally, hypertrophy and hyperplasia of parietal epithelial cells and periglomerular proliferation of myoepithelial arterioles were observed. Multifocally, within tubules, there is homogenous eosinophilic material (proteinuria), rare erythrocytes (hematuria), and rare intratubular karyorrhectic debris. A greyish material deposit was observed on tubular basement membrane and tubular epithelium (calcification). Interstitial lesions include aggregates of plasma cells, lymphocytes and fibrosis.

PAS staining: glomerular hypercellularity with both mesangial and endocapillary proliferation. Glomerular basement membranes are thickened.

Gomori Staining: multifocally, there are red dots in podocyte cytoplasm and basement membrane, and there are fibrotic glomerular and interstitial changes.

Morphologic Diagnosis:  

Kidney: glomerulonephritis, membranoproliferative, diffuse, marked, chronic, with proteinuria, glomerular microcysts and fibrotic changes.
Kidney: interstitial nephritis, lymphoplasmocytic and fibrotic, mild, multifocal, chronic.

Lab Results:  

Clinical laboratory data oriented on chronic renal insufficiency with significant proteinuria suggesting a glomerular involvement. (BUN 38 md/dL; Creatinine 3.9 mg/dL; Albuminemia 2.0 g/dL; Proteinemia 3.9 g/dL; Proteinuria 0.48 g/dL; RPCU 8.6; Du=1.018). Blood count revealed a severe anemia, mildly regenerative, macrocytic with polychromasia, acanthocytes and schistocytes, compatible with an intravascular hemolytic process.

Condition:  

Glomerulonephritis

Contributor Comment:  

Glomerular disease is major cause of chronic kidney disease in dogs. It results from alteration of the glomerular filtration barrier, which includes fenestrated endothelial cells, glomerular basement membrane, epithelial slit pores formed by podocytic processes.(3)

Defects in the glomerular selective filtration result in proteinuria and renal insufficiency, whose clinical spectra ranges from asymptomatic or proteinuric dogs, to non specific presentation (weight loss, apathy, anorexia), or evident signs of chronic renal insufficiency (polyuria, polydipsia, vomiting, halitosis).(6) Extrarenal complications of glomerular diseases include: nephrotic syndrome (hypoalbuminemia, proteinuria, hypercholesterolemia, edema, serous effusions); thromboembolism, secondary to loss of antithrombin III; hypertensive illnesses; and microangiopathic anemia.(2,6)

Glomerular diseases can be acquired or congenital. Acquired glomerular injuries can result from:

1. Immune complex deposition (glomerulonephritis proliferative, membranous, membranoproliferative). Etiologies range from chronic infections (canine pyometra, Borrelia burgdoferi, etc.) to immune-mediated diseases (systemic erythematous lupus).(3)
2. In situ Immune complex formation (anti-GBM glomerulonephritis). Antibodies bind on GBM antigens. It is rare in domestic animal, and suspected in several dogs. In humans, antibodies cross-reaction occurs by antigenic mimicry between streptococcus and GBM for instance.(3,6)
3. Damage by systemic factors affecting the glomeruli. It includes mesangial deposits like amyloidosis, focal segmental glomerulosclerosis, and minimal change disease.(6)

Congenital glomerulopathy gathers an increasing number of breeds, whose pathogeny and mode of inheritance often remains unknown and varies a lot between breeds. The table lists dog breeds with reported familial glomerulopathies.(3)

Breed	Glomerulopathy
Beagle	Amyloidosis Membranoproliferative glomerulonephritis
Bernese mountain dog	Membranoproliferative glomerulonephritis
Bull terrier	Hereditary nephritis
Bullmastiff	Focal and segmental glomerulosclerosis
English cocker spaniel	Hereditary nephritis
Dalmatian	Hereditary nephritis
Doberman pinscher	Glomerulosclerosis Cystic glomerular atrophy
English foxhound	Amyloidosis
French mastiff	Juvenile glomerulopathy
Greyhound	Glomerular vasculopathy and necrosis
Newfoundland	Glomerulosclerosis
Pemprobe Welsh corgi	Cystic glomerular atrophy
Rottweiler	Atrophic glomerulopathy
Samoyed	Hereditary nephritis
Shar-Pei	Amyloidosis
Soft-coated wheaten terrier	Proliferative and sclerosing glomerulonephritis

In Bernese Mountain Dogs, a familial glomerulopathy was reported by Minkus and collaborators in 1994. Lesions included membranoproliferative glomerulonephritis, with concomitant interstitial nephritis and high titer of IgG against Borrelia burgdorferi.(4) Since then, few reports were published, but one of them highlights an absence of correlation between proteinuria, the early sign of glomerular lesions, and the antibodies against B.burgdoferi.(1)

The present case deals with a 2.5-year-old Bernese mountain dog with chronic renal insufficiency and histologic lesions compatible with membranoproliferative glomerulonephritis and interstitial nephritis; however, immunofluorescence should have been performed to confirm it. A proliferation of myoepithelial periglomerular artierioles was also suspected and supports a probable hypertensive state that has not been clinically evaluated.

JPC Diagnosis:  

Kidney: Glomerulonephritis, membranoproliferative, diffuse, marked, chronic, with glomerulosclerosis, fibrosis, tubular mineralization, and mild lymphoplasmacytic nephritis. 

Conference Comment:  

The contributor has provided an excellent and concise overiew of glomerular disease as well as its specific manifestation in the Bernese Mountain dog. Glomerulonephritis is most commonly caused by immune-mediated mechanisms and occurs in three distinct patterns. Proliferative glomerulonephritis is characterized by increased cellularity and is the most common variant observed in horses, usually due to equine infectious anemia or streptococcal antigen. In membranous glomerulonephritis, thickened basement membranes are the predominant change which most commonly occurs in cats. This case is representative of the membranoproliferative form of glomerular disease as most commonly observed in dogs.(5) Collectively, these conditions are generally acquired from accumulations of immune complexes due to low pathogenicity chronic infections with persistent antigenemia.(3) The contributor also highlights those recognized familial forms of glomerular disease in dogs which usually arise in younger animals as a result of various mutations affecting collagen formation or other unidentified mechanisms.(3,4)

References:

1. Gerbe, B, Eichenberger S, Haug K, Wittenbrink MM, & Reusch CE (2009). Association of urine protein excretion and infection withBorrelia burgdorferisensu lato in Bernese Mountain dogs. Vet J, 182(3), 487-488.

2. Kumar V, Abbas AK, Fausto N, & Aster JC (2009). Robbins and Cotran Pathologic Basis of Disease, Professional Edition: Expert Consult-Online. Elsevier Health Sciences.

3. Maxie MG, Newman SJ. Urinary system. In : Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed. Vol. 2. Philadelphia, PA : Elsevier Saunders ; 2007 :459-461.

4. Minkus G, Breue, W, Wanke R, Reusch C, Leuterer G, Brem G, & Hermanns W (1994). Familial nephropathy in Bernese mountain dogs. Vet Pathol, 31(4), 421-428.

5. Newman SJ. The urinary system. In : Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO : Elsevier Mosby ; 2012 :620-627.

6. Vaden SL (2011). Glomerular disease. TopCompanion Anim Med, 26(3), 128-134.

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4-1. Kidney

4-2. Kidney

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