Amyloidosis encompasses a wide variety of diseases that can affect any tissue in the body. Amyloid is an insoluble, waxy aggregate of proteinaceous fibrils (protein chains). The kidney is the most common site of amyloid deposition in the dog. There are many different types of amyloid proteins, but they all are structurally similar and exhibit similar properties in the body and when evaluated under a microscope.
In health, acute inflammation in the body stimulates amyloid protein production by the liver. Circulating amyloid (called Serum Amyloid A, or SAA) exists as microscopic proteins in the blood stream. If there is excessive or chronic production of SAA, it can sometimes lead to these proteins binding together to form chains or fibrils.
Due to the high blood flow and small blood vessels in the kidneys, they are a common place for amyloid fibril deposition. This build up of protein cannot be cleared by the body’s normal clean-up mechanisms, and eventually it will begin to affect the kidney’s normal function.
Most commonly in the Bracco Italiano, the amyloid deposition occurs in the section of the kidney called the glomerulus. This section is responsible for making sure that blood proteins stay in the bloodstream and are not spilled into the urine. Thus, when there is damage to the glomerulus, you can see protein loss in the urine (proteinuria).
Bracchi with amyloidosis do not always have abnormal kidney values (Creatinine, Urea Nitrogen, SDMA) on bloodwork, but many of them have protein loss in the urine.
Another section of the kidney that can be affected are the tubules. These are generally responsible for concentrating urine. The tubules can be directly damaged by amyloid deposition or indirectly from the stress to them caused by ongoing glomerular damage.
While we primarily see amyloidosis as a kidney problem (because that’s where the symptoms are usually seen), it often reflects a systemic disease. In the Shar Pei (and possibly the Bracco Italiano), there is an underlying auto-inflammatory condition that precedes amyloidosis. The trigger is unknown, but there is an increased level of inflammation in the body which predisposes to the amyloid production as described above. This is different than an auto-immune disease, because the immune system is not attacking the body’s own cells and tissues. In a way, amyloidosis could be considered a very messy and destructive byproduct of chronic inflammation.
Amyloidosis is most often diagnosed in young to middle aged Bracchi Italiani. It has been diagnosed in dogs as young as 13 months of age, and as old as 10 years. Most commonly, it is diagnosed around 5 years of age. The range in age may be due to variability in how the disease is inherited or how it progresses. Protein loss in the urine, improperly concentrated urine, or increased kidney values on bloodwork in a young to middle-aged Bracco would be concerning for hereditary kidney disease.
We have not seen any increased risk by sex or color pattern (orange-white and brown-white appear equally affected). It has been diagnosed in many different breeding lines from many countries. We know that it is passed from generation to generation and runs in family lines, although we have not (yet) identified a genetic marker or determined how it is inherited. Due to the complexity of the underlying disease and the small gene pool of the Bracco Italiano, I do not feel that simple pedigree analysis will be adequate to evaluate inheritance.
The presenting symptoms are highly variable. The most common presenting symptom is loss of appetite. Some dogs have increased thirst/urination and weight loss but not all. Seemingly unrelated symptoms (such as joint pain, coughing, and eyelid swelling) have been seen in dogs diagnosed with amyloidosis. This proves the importance of a thorough diagnostic investigation, including urinalysis, for any sick Bracco Italiano.
Most Bracchi Italiani with amyloidosis are proteinuric (have protein loss in the urine). The proteinuria can be very severe. Some complications seen with severe proteinuria include decreased blood protein levels (low albumin, which can lead to edema of the limbs and face, and fluid build up in the abdomen or chest) and an increased risk of abnormal blood clots (thromboembolism, which can affect the lungs, brain, heart, or kidney and result in respiratory distress or sudden death). A couple of dogs have had joint inflammation associated with their disease, similar to Shar Pei Fever (swollen hock syndrome).
Many dogs have a decreased blood albumin level. This could be related to underlying inflammation and/or protein loss in the urine. Some dogs may have increased white blood cell counts or anemia. Abdominal ultrasound is often largely unremarkable, although the kidneys may show a mild loss of their normal layering (called decreased corticomedullary distinction).
As stated above, most Bracchi have amyloid deposition in the glomerulus of the kidney. The tubules are usually also affected, either directly by amyloid deposition (less common) or secondary inflammation (more common). Many dogs have chronic kidney disease changes when their kidney tissue is evaluated under a microscope. Deposition of amyloid in other body tissues is possible, and it is unknown what portion of Bracchi have systemic amyloidosis.
In ongoing research, roughly 13% of apparently healthy Bracchi Italiani had evidence of kidney disease on a single routine screening performed at a national breed event in the USA. The normal prevalence of kidney disease in a population of dogs is closer to 0.4%.
The survival time for amyloidosis is poor once the dog becomes symptomatic. In our initial results, we found that the median survival time after diagnosis (half of the dogs lived longer, half did not survive as long) was 75 days. More severely affected dogs lived only days or weeks after diagnosis. If intervention is achieved before they show symptoms, survival times may be significantly improved with treatment. There is no cure for amyloidosis, and it is considered ultimately life limiting for most dogs diagnosed with the disease.