Glomerulonephritis (GN) in Dogs

Overview of Canine Glomerulonephritis

Glomerulonephritis, commonly abbreviated as “GN”, is a disease of the kidney that can occur in dogs. The kidneys consist of many thousand microscopic filtering units called glomeruli that filter water and small substances from the bloodstream. The tubules of the kidney then reabsorb vital substances such as glucose and electrolytes from the filtered fluid leaving unneeded substances and a small amount of water in the urine.

Glomerulonephritis is inflammation of these microscopic filtering units of the kidneys that develops when immune complexes (complexes of antibodies and antigens) become trapped in the glomeruli, leading to activation of the body’s inflammatory defense system, which, in turn, damages the glomeruli. The immune complexes often form as a consequence of some other disease process such as infection or cancer. However, in many dogs with glomerulonephritis, the inciting cause cannot be found and the problem is said to be idiopathic.

Glomerulonephritis results in excessive loss of protein into the urine (proteinuria). The finding of protein in the urine on urinalysis may be the first indication that your pet has glomerulonephritis. Untreated, the disease can lead to chronic kidney failure.

Dogs of any age, breed or gender can develop glomerulonephritis. In many pets, there may be no obvious symptoms of glomerulonephritis.

What to Watch For

Signs of Glomerulonephritis in Dogs may include:

• Swelling of the abdomen
• Swelling of the paws, hocks (ankles), face or scrotum
• Increased water consumption
• Increased urination
• Weight loss
• Lethargy
• Vomiting
• Sudden loss of vision
• Sudden difficulty breathing

Diagnosis of Glomerulonephritis in Dogs

Diagnostic tests are needed to identify acute glomerulonephritis and exclude other diseases. These may include:

• Urinalysis to identify proteinuria or hyaline casts, which are protein molds of the renal tubules.
• Complete blood count (CBC) to identify anemia, inflammation, infection or low platelet count.
• Serum biochemistry tests to identify low blood protein concentration and high blood cholesterol concentration
• Urine protein/creatinine ratio to determine the severity of protein loss in the urine
• Blood pressure measurement to identify systemic hypertension
• Kidney biopsy to identify glomerulonephritis conclusively and differentiate it from amyloidosis, which is another kidney disease that affects the glomeruli.

Treatment of Glomerulonephritis in Dogs

• The ideal treatment for glomerulonephritis is to identify any underlying infectious, inflammatory or cancerous disease that may be causing production of immune complexes that are being trapped in the glomeruli. Unfortunately, in many cases of glomerulonephritis, no underlying disease process can be identified, or if one can be identified, it cannot be eliminated.
• Immunosuppressive drugs can be administered to suppress immune complex formation. Drugs used for this purpose are cortisone-like drugs like prednisone) and the anti-metabolite drug called azathioprine. This is is not common practice as there has been no scientific evidence that this is beneficial in dogs.
• A very low dose of aspirin may be prescribed to prevent clotting within the glomeruli.
• Specialized diets may be used in some instances.
• Low protein, low phosphorus diets should be given to pets in kidney failure.
• Low sodium diets should be given to pets with hypertension.
• Diets supplemented with omega-3 fatty acids to limit the inflammatory response.
• Medications may be prescribed to control blood pressure in pets that are hypertensive.
• Drugs called angiotensin converting enzyme (ACE) inhibitors like enalapril) may be used to minimize protein loss in the urine and to help control blood pressure.

Home Care and Prevention

Administer as directed any medications prescribed by your veterinarian. Follow any dietary recommendations and schedule regular follow-up visits with your veterinarian to monitor your pet’s progress.

Observation is important. Make sure your dog’s activity level, appetite and attitude remain normal. Watch for difficulty breathing or limb weakness that may indicate development of thromboembolism. Observe your pet for loss of vision that could indicate complications of hypertension. Look for swelling of the paws, hocks or face that could indicate development of subcutaneous edema and for swelling of the abdomen that could indicate fluid accumulation.

Glomerulonephritis is difficult to prevent. Certain infectious, inflammatory and cancerous diseases can lead to development of glomerulonephritis and regular annual examinations by your veterinarian are advised to be certain your pet remains healthy and free of such diseases.

In-depth Information on Canine Glomerulonephritis

The kidneys filter water and small molecules from the bloodstream and into the renal tubules. Water and essential molecules are reabsorbed from the tubules and the remaining waste products and a small amount of water are excreted as urine. The microscopic filters of the kidney are called glomeruli (singular, glomerulus), which are small tufts of capillary blood vessels that act as a sieve, allowing small substances to pass through while keeping larger substances such as proteins and blood cells in the bloodstream.

Glomeruli can be damaged by inflammation and become leaky. This is called glomerulonephritis. Very large things, such as red and white blood cells, still are not filtered but some substances not normally filtered like proteins leak through the inflamed glomeruli into the urine. The excessive loss of protein in the urine is called proteinuria, and this condition can adversely affect your pet’s health.

Glomerulonephritis occurs when large numbers of immune complexes – these are antigen-antibody complexes – circulating in the bloodstream become trapped in the glomeruli as they attempt to pass into the urine. Deposition of immune complexes triggers an inflammatory reaction that damages the glomeruli and results in proteinuria. The antigens bound to the antibodies in the immune complexes arise as a result of some chronic infectious, inflammatory or cancerous disease process. Several diseases have the potential to result in glomerulonephritis.

The clinical symptoms of glomerulonephritis are quite variable.

• Affected dogs may have no symptoms at all. In this instance, glomerular disease first is suspected by the finding of proteinuria on a routine urinalysis.
• Some dogs may have signs of chronic kidney failure such as poor appetite, lethargy, weight loss, poor hair coat, excessive urination and excessive water consumption.
• Some dogs may have symptoms related to sudden blockage of major blood vessels by a blood clot (thromboembolism). Vessels commonly blocked include the lung arteries, which causes rapid breathing or panting, rapid heart rate and high body temperature, and iliac arteries, which causes sudden loss of use of the rear limbs. Thromboembolism is a medical emergency and your pet should be seen by a veterinarian promptly.
• Some dogs may have symptoms related to systemic hypertension. Often the first symptom recognized is acute onset of blindness due to detachment of the retina or bleeding into the retina. This complication is a medical emergency and your pet should be seen by a veterinarian promptly.
• Some dogs may have symptoms of an underlying infectious, inflammatory or cancerous disease process that predisposes the animal to glomerulonephritis.
• Some dogs may have symptoms of subcutaneous edema, including swollen paws, face, hocks (ankles) or scrotum in males, or a swollen abdomen caused by fluid accumulation, known as ascites.

Causes of Glomerulonephritis in Dogs

• Viral infections
• Infectious hepatitis in dogs (canine adenovirus 1)
• Bacterial infections
• Lyme disease (borreliosis)
• Ehrlichiosis (an infectious disease transmitted by ticks)
• Rocky Mountain Spotted Fever (another disease transmitted by ticks)
• Brucellosis (an infectious disease)
• Dermatitis (infection of the skin)
• Gingivitis (infection of the gums)
• Endocarditis (infection of the heart valves)
• Prostatitis (infection of the prostate)
• Pyometra (infection of the uterus)
• Chronic fungal infections
• Heartworm disease
• Leishmaniasis (a protozoal infection rarely encountered in the United States and transmitted by sandflies)
• Non-infectious inflammatory diseases that have been associated with glomerulonephritis include:
• Pancreatitis (inflammation of the pancreas)
• Immune-mediated polyarthritis (inflammation of the joints)
• Systemic lupus erythematosus (an autoimmune disorder)
• Neoplasia (cancer)
• Lymphosarcoma
• Mast cell tumor
• Other tumors
• Despite the long list of infectious, inflammatory and neoplastic disease processes that can result in glomerulonephritis, in as many as 75 to 80 percent of dogs and cats with glomerulonephritis, the underlying cause cannot be identified and the disorder is referred to as “idiopathic.”
• Many other medical problems can lead to symptoms similar to those encountered in pets with glomerulonephritis. It is important to exclude these conditions before establishing a definitive diagnosis.

Veterinary care should include diagnostic tests and subsequent treatment recommendations.

Diagnosis In-depth of Glomerulonephritis in Dogs

Diagnostic tests are needed to recognize mast cell tumors and exclude other diseases that may cause similar symptoms in dogs. These may include:

• A complete medical history and thorough physical examination of your dog.
• A complete blood count (CBC or hemogram) to evaluate for anemia, inflammation, infection or low platelet count. A low platelet count would prompt suspicion of rickettsial diseases such as Ehrlichiosis and Rocky Mountain Spotted Fever. A low blood protein concentration also may be identified on the blood count.
• A serum biochemical profile to evaluate for the presence of low serum albumin concentration (hypoalbuminemia) and high serum cholesterol concentration. Albumin is one of the most important proteins in blood and the first to be affected by protein loss in the urine in pets with glomerulonephritis. These biochemistry findings are very common in dogs with glomerular disease. Other tests on the biochemical profile, such as creatinine, blood urea nitrogen and phosphorus, allow your veterinarian to assess your pet’s kidney function. Finally, other tests on the serum biochemical profile allow your veterinarian to assess the general health of your pet and the possible effects of glomerulonephritis on other body systems.
• Urinalysis to identify proteinuria and evaluate your dog’s kidney function. Hyaline casts may be found in the urine of pets with glomerulonephritis.
• Urine protein/creatinine ratio to quantitate excessive protein loss in the urine and to determine if your dog’s proteinuria is severe enough to justify suspicion of glomerulonephritis. The severity of protein loss with glomerulonephritis is exceedingly variable, and it is possible for an animal to have glomerulonephritis without having a markedly increased urine protein/creatinine ratio. Also, if kidney filtration function worsens with progression of disease in some patients, the urine protein/creatinine ratio will decrease making it less useful as a diagnostic tool. On the other hand, if kidney filtration function remains relatively normal, a decrease in the urine protein/creatinine ratio is a favorable sign indicating clinical improvement.
• A special test called serum antithrombin III concentration to assess the risk of thromboembolism or bloodclot in dogs with glomerulonephritis. Dogs with low serum antithrombin III concentration are at increased risk of thromboembolism.
• A heartworm test and other serum antigen or antibody tests such as borrelia and ehrlichia to search for underlying infectious diseases that may be causing glomerulonephritis.
• Immune function tests such as antinuclear antibody (ANA) or LE prep tests if systemic lupus erythematosus is suspected.
• Needle aspiration of a joint and microscopic analysis of obtained fluid in immune-mediated polyarthritis is suspected.
• X-rays of the chest and abdomen to screen your pet for underlying infectious, inflammatory or neoplastic diseases.
• Abdominal ultrasound examination to evaluate kidney structure and to evaluate other internal organs like the liver and spleen.
• Ultimately, definitive diagnosis of glomerulonephritis requires kidney biopsy which can be performed under ultrasound guidance to minimize risk of complications and ensure an adequate tissue sample. Ideally, one kidney biopsy should be taken for routine light microscopic examination and additional samples should be taken to identify immune complexes using fluorescence and electron microscopy. The latter are very specialized tests that require special sample handing and processing by specialized diagnostic laboratories.

Treatment In-depth of Glomerulonephritis in Dogs

Treatment of glomerulonephritis must be individualized based on the severity of your dog’s condition and other factors that must be analyzed by your veterinarian.

The most effective and specific treatment for glomerulonephritis is elimination of the offending antigens whether they be infectious agents or tumor antigens. Unfortunately, the underlying disease process or antigen source is identified in only 15 to 25 percent of pets with glomerulonephritis and, even if identified, the antigen may be impossible to eliminate, as in the case of lupus erythematosus and some tumor antigens. If the underlying antigen cannot be identified, treatment for idiopathic glomerulonephritis may include:

• Immunosuppressive drugs to suppress antibody formation and production of antigen-antibody complexes. Immunosuppressive drugs aren’t always effective in pets with glomerulonephritis but often are tried. Drugs commonly employed are prednisone (a cortisone-like drug) and azathioprine (an anti-metabolite drug). Other immunosuppressive drugs that have been tried include cyclosporine and cyclophosphamide. Of all of these drugs, azathioprine seems to produce the best results with the fewest adverse effects.
• A very low dosage of aspirin (0.5 to 5 milligrams per kilogram of body weight) has been recommended to reduce the inflammation and blood clotting in the glomeruli. Treatment with aspirin also may reduce the risk of thromboembolism, but this beneficial effect has not been proven in dogs with glomerulonephritis.
• Dietary changes. At one time, it was believed that protein lost in the urine should be replaced with an equivalent amount of protein in the diet. Unfortunately, this approach merely leads to aggravation of the proteinuria. Providing a diet slightly reduced in protein will substantially reduce the magnitude of proteinuria. Dietary sodium restriction also is recommended due to the tendency of dogs with glomerulonephritis to retain sodium and develop hypertension. Lastly, omega-3 fatty acid supplementation may reduce glomerular inflammation and proteinuria. Fish oil is rich in omega-3 fatty acids and some commercial pet foods, designed for medical management of specific diseases, are supplemented with omega-3 fatty acids. Consult your veterinarian for dietary recommendations for glomerulonephritis.
• Angiotensin converting enzyme (ACE) inhibitors. The hormone angiotensin II causes contraction of specific glomerular blood vessels such that proteinuria is worsened. The increased movement of protein across the glomerular blood vessels contributes to progression of disease by promoting scarring of the glomeruli (glomerular sclerosis). ACE inhibitors reduce the production of angiotensin II thereby reducing the blood pressure within the glomeruli. Treatment with ACE inhibitors reduces the amount of protein lost in the urine and may slow the progression of disease. Enalapril is the ACE inhibitor most commonly used for this purpose.
• Anti-hypertensive drugs. If systemic hypertension is present and persists despite dietary sodium restriction and treatment with enalapril, other anti-hypertensive medications may need to be employed.
• Diuretics. Pets that develop severe ascites or subcutaneous edema may require treatment with diuretic drugs to facilitate mobilization and excretion of salt and water in the urine. Furosemide is the diuretic most commonly recommended in this situation. Caution should be used to be certain that the animal does not become dehydrated while being treated with furosemide.

Follow-up Care for Dogs with Glomerulonephritis

Optimal treatment for your dog requires a combination of home and professional veterinary care. Follow-up can be crucial. Administer as directed any medications prescribed by your veterinarian and contact your veterinarian promptly if you have difficulty treating your pet.

Follow dietary recommendations for your dog made by your veterinarian. Dogs with glomerulonephritis often are placed on a low-protein, low-sodium diet and omega-3 fatty acid supplementation may be recommended.

Observe your dog’s activity level and appetite and watch for signs of complications including swelling of the limbs or abdomen indicating subcutaneous edema or ascites, sudden loss of vision indicating possible retinal hemorrhage or detachment secondary to hypertension, or sudden onset of difficulty breathing or loss of use of the rear limbs potentially indicating thromboembolism.

Actual prescribed follow-up depends on the severity of your pet’s disease, response to therapy and your veterinarian’s recommendations. Your veterinarian will monitor protein loss in the urine by periodically evaluating your pet’s urine protein/creatinine ratio. Your veterinarian will monitor serum biochemistry on your pet to determine if blood proteins, including albumin, are increasing, cholesterol is decreasing, and to be sure that renal function (creatinine, blood urea nitrogen, phosphorus) remains stable.

Systemic blood pressure should be monitored in dogs with glomerulonephritis, especially if your pet is being treated with an ACE inhibitor such as enalapril.

Close monitoring of dogs with glomerulonephritis is crucial because the outcome is very variable. Pets with this disorder follow one of three clinical courses:

• Resolution of the disease with return to normalcy. This course is most likely in pets with normal kidney filtration function (normal creatinine and blood urea nitrogen).
• Smoldering disease that doesn’t improve or progress with persistently high urinary excretion of protein.
• Progression of disease to end- stage kidney failure over a matter of months to years.