Definition

• Inflammation and progressive dysfunction of glomeruli. Commonly a consequence of intraglomerular immune complex deposition; with or without inflammatory cell infiltration.
• “Glomerulonephritis” (GN) should not be used as an umbrella term for all glomerular diseases, as glomerular injury may be initiated and progress without inflammation.
• Circulating antigen-antibody complexes may be deposited or trapped within glomeruli. Alternatively, immune complexes may form within the glomerular capillary wall when circulating antibodies react with “planted” antigens. Immune complexes activate complement and induce leukocyte infiltration, platelet aggregation, and fibrin deposition, all of which may contribute to glomerular damage; urinary loss of serum proteins and macromolecules also contribute to progressive tubular damage.
• Progressive cellular proliferation and glomerular basement thickening may progress to glomerular hyalinization and sclerosis, nephron loss, and azotemic CKD.

Systems Affected

• Renal/Urologic-initial proteinuria with few or no white or red blood cells. With progressive disease, azotemia and uremic CKD occur.
• Cardiovascular-edema and ascites secondary to hypoalbuminemia and sodium retention may develop. Hypertension is common. Hypercholesterolemia and hypercoagulability may result in thromboembolic disease.

Genetics

• Familial GN has been reported in Bernese mountain dogs, Brittany spaniels, bull terriers, bullmastiffs, French mastiffs, Dalmatians, Samoyeds, Doberman pinschers, cocker spaniels, Newfoundlands, rottweilers, Pembroke Welsh corgis, beagles, and soft-coated Wheaten terriers.

Incidence/Prevalence

Subclinical glomerular disease is common in dogs. Up to 90% of random-source dogs have glomerular lesions noted on necropsy.

Signalment

Signs

Causes

• True auto-immune GN, in which antibodies target a native renal antigen, is rarely found in dogs and cats.
• Numerous infectious and inflammatory diseases associated with glomerular immune complex deposition or formation (see below). In many dogs and cats, however, no antigen source can be identified, and glomerular disease is considered idiopathic. Diseases associated with glomerulonephritis include:
  • Dogs-infectious diseases (anaplasmosis, babesiosis, brucellosis, dirofilariasis, ehrlichiosis, hepatozoonosis, infectious canine hepatitis, leishmaniasis, pyometra, borreliosis, chronic bacterial infections such as endocarditis and discospondylitis, trypanosomiasis); neoplasia; inflammatory diseases (e.g., systemic lupus erythematosus); endocrinopathies (hyperadrenocorticism, diabetes mellitus, long-term administration of corticosteroids); hereditary nephritides; miscellaneous causes (sulfonamides).
  • Cats-infectious diseases (e.g., FeLV, FIP, FIV, Mycoplasma polyarthritis); neoplasia.

Differential Diagnosis

• Proteinuria-commonly due to inflammation of the post-glomerular urinary tract (e.g., bacterial cystitis/pyelonephritis, urolithiasis, tubular renal failure, neoplasia). Lower urinary tract inflammation is usually (but not always) associated with active urine sediment. Hyperglobulinemia may result in proteinuria, particularly when the sulfosalicylic acid turbidimetric test is used for protein detection. Like glomerulonephritis, renal amyloidosis often causes severe proteinuria with inactive urine sediment. Renal biopsy is the only accurate method for differentiating the various glomerular disease subtypes.
• Hypoalbuminemia-may result from decreased albumin production (liver disease) or gastrointestinal loss (protein-losing enteropathies).

CBC/Biochemistry/Urinalysis

• CBC usually unremarkable.
• Hypoalbuminemia and hypercholesterolemia occur in severe cases.
• Persistent proteinuria with inactive urine sediment (although hyaline casts may be noted).
• Microalbuminuria oftentimes precedes overt proteinuria, and may allow early detection of glomerular damage.
• With progressive glomerular disease, biochemical changes consistent with renal failure develop. Azotemia may precede complete loss of urine concentrating ability.

Other Laboratory Tests

Imaging

May be helpful when screening for initiating inflammatory, neoplastic, or infectious diseases. Mild renomegaly may be observed.

Diagnostic Procedures

• Permits differentiation of the various histologic subtypes of glomerular disease. Biopsy results may influence treatment recommendations, and provide prognostic information. Renal biopsies should be considered only once less invasive tests (e.g., CBC, serum biochemistry profile, urinalysis, and quantitation of proteinuria (UPC)) have been completed, and if coagulation testing is normal.
• Relative contraindications: a solitary kidney, thrombocytopenia or other coagulopathies, renal lesions associated with fluid accumulation (e.g., hydronephrosis and renal cysts and abscesses).
• Biopsy-related complications are more likely in dogs or cats weighing <5 kg, or with severe azotemia.

Pathologic Findings

• Varying severity of GBM thickening (membranous) and increased mesangial cellularity (proliferative); glomerular scarring may be noted (glomerulosclerosis).
• Biopsy tissue should be placed in special fixatives and preservatives at the time of collection rather than in formalin. Immunofluorescent and/or immunohistochemical staining and electron microscopy maximize the information gained from evaluation of renal biopsies.

Diet

Sodium-reduced, high-quality, low-quantity protein diets are usually recommended. Most prescription “renal” diets meet these criteria.

Client Education

Once azotemia and uremia occur, prognosis is guarded to poor due to rapidly progressive disease.

Drug(s) Of Choice

• The most specific and effective therapy is elimination of any source of antigenic stimulation. In most dogs the initiating disease or antigen source cannot be definitively identified, or may be impossible to eliminate (e.g., neoplasia).
• ACE inhibitors reduce proteinuria by altering glomerular filtration pressure. Enalapril (0.5 mg/kg q12–24h) has antihypertensive and antiproteinuric effects and slows renal disease progression in dogs with naturally-occurring idiopathic GN. Because proteinuria is directly toxic to renal tubules, ACE-inhibitor therapy should be initiated at the time of initial disease diagnosis unless severe azotemia is present.
• No controlled veterinary clinical trials have demonstrated a beneficial effect from immunosuppressive therapy, despite inflammation being a consequence of an inappropriately activated immune system. Glucocorticoids and cyclosporine have independently been shown to worsen proteinuria and prognosis in some patients.
• Aspirin decreases pro-inflammatory thromboxane production. Low-dose aspirin (0.5 mg/kg PO q12–24h) may decrease platelet aggregation and prevent reductions in beneficial prostaglandins. Aspirin therapy should be initiated once serum albumin is <2.2–2.5 g/dL, or when serum antithrombin is known to be decreased (regardless of albumin concentration).

Contraindications

Some glomerular disease subtypes, particularly membranous glomerulopathy prior to onset of azotemia, may favorably respond to immunosuppressive drugs. Biopsy is recommended prior to attempting immunosuppressive therapy. If a biopsy cannot be obtained, then immunosuppression can be considered in dogs with serum creatinine >3.0 mg/dL, progressive azotemia, or severe (<2.0 g/dL) hypoalbuminemia and inadequate responses to standard therapy alone.

Precautions

• Dosages of highly protein-bound drugs and/or drugs eliminated by the kidneys (e.g., aspirin) may require adjustment.
• ACE inhibitors should be used cautiously in azotemic patients. Once serum creatinine is approx. >3.5 g/dL, reduced ACE inhibitor doses should be considered. Serum creatinine should be monitored 4–7 days after dosage increase to evaluate the status of azotemia.

Patient Monitoring

• UPC-is the least invasive method to assess progression or remission of GN.
• Magnitude of proteinuria will also decrease as nephrons are lost to progressive disease, interpret changes in the UPC ratio in light of serum creatinine changes.
• Monitor serum urea nitrogen, creatinine, albumin, and electrolyte concentrations, blood pressure, and body weight at each evaluation.
• Ideal reexamination schedule in stable patients is 1, 3, 6, 9, and 12 months after initiation of treatment.

Prevention/Avoidance

Do not breed animals with suspected familial disease.

Possible Complications

• Nephrotic syndrome
• Hypertension
• Chronic renal insufficiency or failure
• Thromboembolic disorders

Expected Course and Prognosis

• Guarded to poor
• Often progress despite treatment

Synonyms

• Glomerulonephropathy
• Protein-losing nephropathy

See Also

• Amyloidosis
• Lyme Borreliosis
• Nephrotic Syndrome
• Proteinuria

Abbreviations

• ACE = angiotensin-converting enzyme
• CKD = chronic kidney disease
• FeLV = feline leukemia virus
• FIP = feline infectious peritonitis
• FIV = feline immunodeficiency virus
• GBM = glomerular basement membrane
• RBC = red blood cell
• WBC = white blood cell

Client Education Handout Available Online