Amyloidosis

David C. Van Metre

Amyloidosis is caused by extracellular deposition of insoluble, fibrillar protein in tissues.¹ Amyloid arises from various precursor proteins that become abnormally folded.

Clinical Signs

Although subclinical deposition of amyloid can occur in a variety of tissues,² in cattle, the kidneys are most commonly affected in clinical disease.^3,4 The most common clinical signs of bovine amyloidosis include chronic diarrhea, weight loss, generalized edema, and poor productivity in mature animals.^3-5 Enlargement of the left kidney may be palpated rectally.⁵ The enlarged kidney is not painful and maintains its normal lobula­tion. Because amyloidosis may develop secondary to an underlying inflammatory disease, such as metritis or traumatic reticuloperitonitis, signs of the primary disease process may be superimposed.

Clinical Pathology

Marked proteinuria and hypoalbuminemia are hallmarks of disease.^3-5 Hyperfibrinogenemia, hyperglobulinemia, and an inflammatory leukogram may reflect the underlying inflam­matory disease. Renal azotemia may exist. Urinalysis reveals persistent, heavy proteinuria. Importantly, a positive reaction for protein on urine dipstick is expected when the urine is alkaline (as is common in cattle); therefore, more specific tests for protein, such as the sulfosalicylic acid precipitation test, should be used to confirm proteinuria. Polarized light microscopy and electron microscopy have been used to detect amyloid protein in urine sediment.⁶ There is no pyuria or hematuria.

Differential Diagnosis

Amyloidosis must be differentiated from other diseases causing chronic diarrhea, hypoproteinemia, weight loss, and poor pro­ductivity.

Pathophysiology

Light-chain (AL) amyloidosis is a rare disorder associated with immune cell dyscrasias, such as multiple myeloma. In AL amyloidosis, the amyloid forms from abnormally folded immunoglobulin light chain.¹ In contrast, bovine amyloidosis is classified as the reactive (AA) type, which is frequently associated with chronic inflammatory disease in domestic animals and humans.^1-5 Most, but not all, cattle with AA amyloidosis have concurrent inflammatory disease, such as traumatic reticuloperitonitis, pneumonia, mastitis, footrot, or metritis. Serum amyloid A protein (SAA) is an acute-phase protein that is synthesized in the liver and is a precursor of amyloid A (AA) fibril in tissues.¹ SAA concentrations increase in cattle with inflammatory disease.³ Some of these cattle may subsequently develop amyloid deposits in organs because of abnormal catabolism, misfolding, and deposition of SAA.¹ Once embedded in tissue, smaller AA fibrils may serve as a nidus for further AA accretion and enlargement of the amyloid deposit.⁷ Accumulation of amyloid in the glomerulus alters glomerular filtration and enables sustained albuminuria and a gradual loss of plasma oncotic pressure. Diarrhea develops as a result of gut wall edema, fluid loss into the gut lumen from the hypooncotic plasma space, and amyloid deposition in the GI tract.⁵

Necropsy Findings

Renal enlargement with yellow-tan to white discoloration is frequently present. A waxy quality of the renal parenchyma may be appreciated on cut surface of the kidney.^3-5 Generalized edema is apparent.

Prognosis

The prognosis for affected cattle is poor. The resilient nature of the amyloid protein generally results in its persistence in tissues, even if the underlying inflammatory disease is treated. Specific treatment for amyloidosis has not been reported in cattle. The potential for cross-species transmission of amyloi­dosis is an area of active research.⁸

Amyloidosis in Other Ruminants

AA amyloidosis has also been reported in domestic sheep and goats, as well as a variety of nondomesticated ruminants.^9-11 It appears to be a consequence of chronic suppurative diseases such as pneumonia,⁹ caseous lymphadenitis,¹⁰ and in lambs, polyarthritis caused by Erysipelothrix rhusiopathiae.¹¹ As for cattle, amyloid deposition can be detected histologically in multiple tissues of affected animals, with gross and histologic lesions primarily involving the kidneys. The clinical course of AA amyloidosis in small ruminants is poorly described but is speculated to be a protein-losing glomerulopathy, akin to the disease in cattle.¹⁰