- In familial renal amyloidosis of shar-peis, deposition of amyloid can progressively disrupt normal renal architecture, leading to chronic kidney disease (CKD).
- Amyloidosis is the extracellular deposition of fibrils formed by polymerization of proteins with a beta-pleated sheet conformation.
- Reactive amyloidosis secondary to chronic infectious and noninfectious inflammatory disease and neoplasia is the most common form in animals.
- Renal amyloidosis can result in CKD, proteinuria, and nephrotic syndrome.
- Many shar-peis will have fever and swelling of the tibiotarsal joints (also called shar-pei fever or shar-pei swollen hock syndrome) before development of renal amyloidosis.
- The cause of this syndrome in shar-peis is unknown.
- Although this disease is considered genetic, not all shar-peis with the trait will develop renal amyloidosis (see Genetic Implications).
- Not all shar-pei fever patients will have renal amyloidosis.
- Renal dysfunction is the most common; however, other organ systems can be affected by amyloid deposition.
- In shar-peis, this is an autosomal recessive trait.
Incidence & Prevalence
- Renal amyloidosis is estimated to occur in 23% of shar-peis in the United States.
- True prevalence is unknown.
- Shar-peis are predisposed.
- Familial renal amyloidosis has also been reported in beagles, English foxhounds, collies, Walker foxhounds, and Abyssinian and Siamese cats.
Age & Range
- Age of onset of clinical signs is typically 1–6 years (mean, 4.1 years).
- More common in female than male dogs (female:male ratio, 2.5:1)
- Amyloid A protein, formed by the polymerization of the amino acid terminal portion of serum amyloid A (SAA) in response to inflammatory cytokines, is the primary protein involved in reactive amyloidosis.
- Affected shar-peis have increased serum concentrations of interleukin-6, a cytokine that stimulates synthesis of SAA and the release from hepatocytes.
- Other cytokines (eg, tumor necrosis factor-α, interleukin-1β) are also involved.
- These cytokines initiate the acute phase response characterized by fever, hepatic production of acute proteins (including SAA), and mobilization of neutrophils.
- Amyloid deposition disrupts normal tissue architecture and can cause organ failure.
- In shar-peis, amyloid deposition can occur in the kidneys, liver, spleen, pancreas, adrenal glands, thyroid glands, myocardium, prostate, lymph nodes, and GI tract.
- Most do not show signs of organ dysfunction other than kidney or hepatic disease.
- Renal amyloidosis in other canine breeds can lead to marked proteinuria.
- Only 25%–43% of affected shar-peis have proteinuria.1
- Nephrotic syndrome—characterized by marked proteinuria, hypoalbuminemia, hypercholesterolemia, and edema—can be present.
- Some affected dogs are at increased risk for thromboembolic disease, in part because of loss of antithrombin through the affected glomerulus.
- A similar syndrome of fever and synovitis called familial Mediterranean fever occurs in humans.
History & Physical Examination
- Intermittent episodes of fever ± joint swelling or pain
- Episodes often precede amyloidosis, although these episodes may not be detected.
- At initial presentation, intermittent high fever (ie, 103°F–107°F) and joint swelling (eg, tibiotarsal joints) that resolve ± treatment may be present.
- Affected patients may appear normal if fever and joint swelling are not present.
- Marked CKD may result in oral ulceration, uremic breath, and dehydration.
- Nephrotic syndrome may result in ascites, SC edema, or both.
- Acute onset of respiratory distress, tachypnea, or pelvic limb paresis may indicate thromboembolic disease.
- Jaundice occurs if hepatic amyloidosis is present.
- Hepatic amyloidosis has been reported in ~11% of cases.2
- Signs include polydipsia, polyuria, anorexia, vomiting, dehydration, weight loss, weakness, and lethargy.
- Renal biopsy specimen should be obtained from the renal cortex to reduce complications (eg, hemorrhage, infarction).
- Because amyloid deposits are often limited to the medulla, the diagnosis may be unobtainable on renal biopsy; however, medulla biopsies are not recommended because of risk for complications.
- Approximately 64% of shar-peis will have glomerular involvement.
- Staining with Congo red (see Figure 1, Renal biopsy specimen stained with Congo red showing typical birefringence of glomerular amyloid deposits. Image courtesy S.P. DiBartola)
- Light microscopy discloses amyloid deposits in various shades of red.
- Polarizing microscopy discloses amyloid deposits in an apple green birefringence.
- Amyloid deposition is confirmed by decolorization of Congo-red–stained deposits by potassium permanganate oxidation.
- If intermittent fever and joint swelling precede onset of CKD signs in a shar-pei, renal biopsy is not recommended.
- Treatment of presumed amyloidosis should be initiated.
- Aspirates from other organs (ie, liver, spleen) can be obtained if positive staining with Congo red is documented.
- Joint disease
- Polyarthritis (ie, immune mediated, bacterial, viral, fungal)
- Lyme disease, especially in endemic areas
- Vaccine reaction
- Renal amyloidosis
- Other glomerular diseases