FELINE GLOMERULAR DISEASES

• 1. What are the two major categories of glomerular disease?

  Glomerulonephritis and amyloidosis.

• 2. How prevalent is glomerular disease in cats?

  Confirmed cases of feline glomerular disease are rare. In two separate surveys of 160 and 333 sick cats, only one suspected case of glomerulonephritis was identified. One review of published reports of feline amyloidosis uncovered 20 cases over a 20-year time span. However, reports of glomerular disease in cats have increased in prevalence with the advent of electron microscopy and the ability to discern changes in basement membrane and podocyte foot process morphology.

• 3. Describe the pathogenesis of glomerulonephritis.

  Glomerulonephritis results from one of two immunologic mechanisms: immune complex deposition or formation of antibodies to glomerular basement membrane components. Soluble, circulating antigen–antibody complexes may become localized in glomerular capillary walls, or in situ immune complexes may be formed in response to antigens within the glomerular basement membrane and capillary walls.

• 4. What glomerular changes result from immune complex deposition?

  The glomerular response to immune complex deposition is glomerular cell proliferation and glomerular capillary wall thickening. Associated findings are cellular and mesangial matrix proliferation and glomerular basement membrane thickening.

• 5. Describe the pathologic progression of glomerulonephritis.

  Antibody–antigen complexes within the glomerulus activate complement, stimulate platelet adhesion and aggregation, signal neutrophil infiltration, and activate the coagulation system. Complement activation triggers an inflammatory response, including the release of proteolytic and lysosomal enzymes by neutrophils, followed by fibrin deposition. Aggregated platelets release thromboxane, which further promotes inflammation.

• 6. What clinicopathological abnormalities are consistent with glomerulonephritis?

  The hallmark abnormality of glomerulonephritis is proteinuria. In addition, an inactive urine sediment is usually present, and both hyaline and granular casts may be observed. Progression of the disease and response to treatment can be monitored by serial measurement of the urine protein:creatinine (UPC) ratio. Hypoalbuminemia and hypercholesterolemia may occur if nephrotic syndrome develops.

• 7. What is a normal UPC ratio?

  A UPC ratio < 1 is considered by many to be normal. However, some clinicians consider a UPC > 0.5 significant in cats. A moderately elevated UPC ratio (i.e., > 1; < 20) is consistent with glomerulonephritis.

• 8. What nonspecific clinical findings are consistent with glomerulonephritis?

  Nonspecific clinical findings associated with glomerulonephritis include anorexia, vomiting, weight loss, and lethargy; edema or ascites (rare in cats) secondary to hypoalbuminemia; azotemia; polyuria and polydipsia secondary to renal failure; hypertension; and hypercoagulability. Evidence of nephrotic syndrome (proteinuria, hypoalbuminemia, ascites or edema, and hypercholesterolemia) should alert the clinician to the possibility of glomerulonephritis. As glomerulonephritis is often secondary to another primary disease process, the clinical presentation may be dominated by the primary disease.

  Primary Disease Processes That May Result in Secondary Feline Glomerular Disease

  Bacterial pyoderma or chronic skin inflammation Dental disease (e.g., chronic gingivitis) Dirofilariasis Ehrlichial infections Endocarditis Feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis, and associated conditions (e.g., lymphoma) Immune-mediated diseases Neoplasia Pancreatitis Pyometra Systemic lupus erythematosus

• 9. Summarize the diagnostic plan for cats with suspected glomerulonephritis.

  Complete cell count, serum biochemical panel, urinalysis with protein/creatinine ratio, and systemic blood pressure are recommended for all cats with glomerulonephritis. Renal ultrasound may be used to evaluate for morphologic renal diseases. Thoracic and abdominal radiographs may be used to evaluate for occult infections or neoplasia. Feline leukemia virus serum antigen test and feline immunodeficiency virus serum antibody test are indicated in most cases. Other specialized testing, such as serum coronavirus antibody titers, Ehrlichia spp. antibody titers, and Dirofilaria immitis serum antigen and antibody tests, are indicated in some cats.

• 10. How is glomerulonephritis diagnosed?

  The definitive diagnosis of glomerulonephritis requires histologic examination of renal biopsy specimens.

• 11. How can renal tissues be collected? What are the risks?

  Because of the availability of ultrasound and the potential for complications, it is no longer advisable to attempt biopsy of renal tissue “blindly.” Ultrasound guidance or direct visualization with laparoscopy or exploratory laparotomy can be used to obtain samples of renal tissue. Excessive bleeding from the biopsy site is a potential complication, especially in animals that are hypertensive. Assessment of platelet count, activated clotting time or other clotting factor assessment, and arterial blood pressure is highly recommended before the procedure is performed. Laparoscopy offers the advantage of being able to apply direct pressure or Gel-foam to the biopsy site if persistent bleeding occurs.

• 12. What necropsy changes are seen with glomerulonephritis?

  Any progressive destruction of nephrons results in gross and microscopic changes in the kidney that appear similar, regardless of the underlying cause. On gross inspection, kidneys are slightly smaller than normal, firm and pale, with irregular pitting and linear fibrosis.

• 13. Describe the histologic appearance of glomerulonephritis.

  Histologic examination of renal tissue confirms medullary and glomerular deposition of eosinophilic hyaline material. In hematoxylin- and eosin-stained sections, glomerular capillary walls are diffusely thickened and intensely eosinophilic. Papillary necrosis, tubular dilatation, lymphocytic-plasmacytic cellular infiltration, and interstitial fibrosis also are seen. The glomerular walls are often thickened and eosinophilic. The periodic acid-Schiff stain is used to highlight small glomerular basement membrane projections consistent with immune complex deposition. Mesangial matrix and cell proliferation can be observed. Continued necrosis and glomerular atrophy lead to end-stage nephron destruction, scarring, fibrosis, and sclerosis.

• 14. What happens if glomerulonephritis is left untreated?

  Without treatment, glomerulonephritis leads to irreversible damage from fibrin deposition and glomerulosclerosis. The loss of nephron function eventually leads to renal insufficiency and failure.

• 15. What are the treatment objectives for cats with glomerulonephritis?

  The first objective of treatment is to identify and treat any underlying disease (i.e., removal of the offending antigen). Unfortunately, this goal is often impossible.

• 16. Are glucocorticoids appropriate for treatment of glomerular disease in cats?

  Unless the primary disease process is a glucocorticoid-responsive condition, glucocorticoids are not recommended for the treatment of glomerular disease. Although cats are considered resistant to most side effects of long-term glucocorticoid use, treated dogs have demonstrated an increase in proteinuria and azotemia as well as loss of body condition. Elevated endogenous or exogenous glucocorticoid levels also predispose the animal to thromboembolic events. Other immunosuppressive drugs used to treat glomerular disease in dogs include azathioprine, chlorambucil, cyclophosphamide, and cyclosporine, but few controlled studies have investigated their efficacy in dogs. Several of these agents may be too toxic for use in cats (e.g., azathioprine).

• 17. What other treatments should be considered for glomerular disease in cats?

  Thromboxane synthetase inhibitors, angiotensin-converting enzyme (ACE) inhibitors, prostaglandin analogs, leukotriene antagonists, and dietary omega-3 fatty acid supplements have been investigated for their ability to reduce glomerular inflammation and associated symptoms (e.g., proteinuria, hypertension). Antiplatelet therapy with low-dose aspirin is a mainstay of treatment for dogs with glomerular disease, but thromboembolic events secondary to glomerular disease are rare in cats. If edema or ascites is present, treatment may include a reduced sodium, protein-restricted diet in addition to an ACE inhibitor. For treatment of significant hypertension (systolic blood pressure > 170–180 mmHg), the calcium antagonist amlodipine (0.625 mg/cat once daily) is the drug of choice (see Chapter 63). Blood pressure should be rechecked at 2–4- week intervals at the start of therapy. The ACE inhibitor enalapril (0.25 mg/kg once daily) or a beta antagonist such as atenolol (6.25 mg/cat once daily) may be added if monotherapy is ineffective, but extreme caution and diligent follow-up are required to monitor for progressive azotemia and renal failure.

• 18. Define renal amyloidosis.

  Amyloidosis is the deposition of fibrillar proteins in various tissues. These proteins assume a beta-pleated sheet configuration, which makes them insoluble and resistant to proteolysis. Amyloid impairs the function of the organ in which it is deposited. Renal amyloidoisis is usually secondary (reactive) to some infectious, inflammatory, or neoplastic disease process.

• 19. How does renal amyloidosis differ in cats and dogs?

  Renal amyloidosis in cats is rare. Feline amyloidosis usually affects the medulla of the kidney, whereas in dogs renal amyloidosis is usually a glomerular disease. Amyloid deposit in the feline kidney results in medullary fibrosis and papillary necrosis. Unlike dogs, severe proteinuria is uncommon in cats because amyloid deposition is interstitial (sparing the glomeruli).

• 20. In what breed of cat does renal amyloidosis have a genetic basis?

  Renal amyloidosis has been diagnosed in a number of related Abyssinian cats. The cats had marked medullary interstitial and glomerular amyloid deposition, interstitial fibrosis, and papillary necrosis. Siamese and Oriental shorthair breeds also have an increased incidence of amyloidosis.

• 21. What clinical and clinicopathologic abnormalities are associated with renal amyloidosis?

  Cats are usually quite sick and often uremic, with nonregenerative anemia, hyperphosphatemia, metabolic acidosis, isosthenuria, and proteinuria. Concurrent amyloid deposits in the liver of Siamese and Oriental shorthair breeds may lead to hepatic rupture and severe, acute hemorrhage.

• 22. Describe the typical progression of renal amyloidosis.

  Amyloid deposits interfere with the blood supply (vasa recta) to the renal medulla, resulting in papillary necrosis. The progressive loss of nephrons leads to renal failure and uremia. Feline amyloidosis carries a grave prognosis. Both dimethylsulfoxide (DMSO) and colchincine have been used to treat canine amyloidosis, but the results are equivocal, and similar studies have not been performed in feline amyloidosis. Both drugs may result in significant gastrointestinal side effects, and neither drug is likely to be of benefit once renal failure is established.