Canine Glomerulonephritis

Most of the time when kidney disease is discussed, renal insufficiency or chronic kidney failure is the subject. In this condition, the kidney loses its ability to conserve the body’s water as it removes the body’s daily toxin build up. Large amounts of water are required to make enough urine. Excessive water consumption is seen as an early sign. Weight loss ensues. There are classical metabolic changes that result.

Glomerular disease is completely different.
The glomerulus is the microscopic kidney area that filters toxins. Its job is to remove all the small metabolic toxins from the blood stream and leave the larger molecules (specifically blood proteins) in the blood stream where they belong. The glomerulus separates urine from blood. Fine tuning occurs later on along the kidney’s tubules where electrolytes are balanced but the initial filtering takes place in the millions of glomeruli making up the kidneys.

In glomerular disease, holes are punched out in this filtration system allowing large molecules that one’s body needs to keep to enter the urine flow and be urinated away into oblivion. In glomerulonephritis, it is chronic inflammation that leads to the holes in the filtration system. A chronic stimulation of the immune system leads to circulating bits of antibody/antigen clumps. These clumps stick in the filtration membranes of the glomerulus where they generate more inflammation and eventually to a small hole.

How Is Diagnosis Made?
Technically a biopsy of the kidney is needed to absolutely confirm this diagnosis but usually urine testing is sufficient to feel confident of glomerular disease. Protein loss in the urine is apparent on a routine urinalysis. A small amount of protein in urine is not abnormal, especially if the urine is well concentrated, but if it seems like the amount of protein may be more than what is expected, further testing is needed. A urine culture to rule out a latent bladder infection is helpful as the inflammation generated by a bladder infection will add protein to the urine. A test called a urine protein:creatinine ratio can be performed on the urine sample to quantify the amount of protein loss more effectively.

If the protein:creatinine ratio is sufficiently elevated, this indicates damage to the glomeruli and that means either glomerulonephritis or a condition called amyloidosis. Only a biopsy of the kidney can determine which is present; however, in amyloidosis (where the kidney is infiltrated by a malignant abnormal protein called amyloid) prognosis is so poor and the progression of disease so rapid that response to treatment can suggest which condition is present.

An important blood test to note is the albumin level. Albumin is an important blood protein responsible for carrying numerous other biochemicals around the bloodstream. When this protein is found to be low on a screening blood test, it is important to determine why. Albumin can be lost (urinated away) in glomerular disease, lost in the intestinal tract in certain GI diseases, or simply under-produced in liver disease. A low albumin level may be the tip off to early detection in glomerular disease and when it is found, a urine protein:creatinine ratio should be done. If the blood albumin level drops too low, edema (fluid accumulation) results, typically in the lower extremities.

What Can Cause Glomerulonephritis?
Any thing that chronically stimulates the immune system can cause this kind of kidney damage. Some common possible causes include:

Long-ignored severe dental disease

Cancer

Heartworm infection 

Ehrlichia infection (a tick-borne disease)

Lyme disease (another tick-borne disease)

infection

Feline infectious peritonitis

Pyometra (abscessed uterus)

Endocarditis (bacterial infection in the heart)

Chronically inflamed skin

Immune-mediated diseases (such as lupus)

Chronic pancreatitis

Prostatitis (inflamed prostate)

Glomerulonephritis can also be idiopathic, which means that despite searching, the underlying cause cannot be found.

Clinical Signs / Symptoms
Most animals with glomerulonephritis lose weight as well as appetite. Upset stomach is common. Approximately 70% of patients will progress to the more classical chronic renal failure, which tremendously worsens the ultimate prognosis.

In severe cases of glomerular disease, a complication called nephrotic syndrome can result due to the extreme urinary protein loss. Patients with nephrotic syndrome develop:

High blood pressure
Tendency to form abnormal blood clots
Edema (swelling) especially of the legs

Nephrotic syndrome is defined as the combination of :
significant protein loss in urine 

low serum albumin 

edema or other abnormal fluid accumulation, and elevated blood cholesterol level. 

Treating This Disease
The most significant thing that can be done in treating glomerulonephritis is to identify the antigen source and eliminate it if it is possible to do so. This means broad testing may be needed to screen for the conditions listed above.

The next most important aspect of treating glomerular inflammation is suppression of the immune system. This means medications such as cyclophosphamide, or cyclosporine. If the underlying condition is corticosteroid responsive (i.e. the cortisone derivatives are indicated) then something like prednisone might help but in most cases prednisone is not a good choice. Chronic corticosteroid use can lead to Cushing’s Syndrome and can increase the risk of abnormal clotting (thromboembolism). The urine protein:creatinine ratio can be monitored for progress. If the ratio increases, this would indicate that immune suppression is not helping and that medication should be changed or even discontinued.

The third part of treatment is about preventing the immune complexes from sticking to the delicate glomerular membranes. Aspirin administration is the simplest way to accomplish this; low doses of aspirin also reduce the tendency towards excessive blood clotting. There is currently research in progress about using omega 3 fatty acid supplementation to further assist in this branch of treatment but specific treatment recommendations have not yet been worked out.

The fourth portion of treatment involves a group of drugs called angiotensin converting enzyme inhibitors (or simply ACE inhibitors). Enalapril is currently the only one approved for use in dogs but numerous ACE inhibitors are available as they are widely used in human medicine. The ACE inhibitors are helpful in that they reduce protein loss and preserve renal function. Further, they can help drop high blood pressure. The problem with the ACE inhibitors is that they inherently drop blood flow to the kidney, which can be a problem if diuretics are used concurrently, as in heart failure. In most cases of glomerular disease, this is not an issue.

Historically, supplementing protein was recommended to compensate for the urinary protein loss. This has since been found to actually make the protein loss worse and is no longer recommended.

Further Resources
Other web pages on this subject that might be helpful:
http://courses.vetmed.wsu.edu/vm552/urogenital/gn.htm
It’s a bit technical as it is meant as veterinary student education but it still has excellent detail.