26th June 2023

Amyloidosis and the kidney

Overview

Amyloidosis is an acquired or inherited disorder of protein folding. Proteins which are normally soluble are deposited in the extracellular space and cause progressive organ dysfunction. The most common type of this is Amyloid A amyloidosis (AA), also referred to as secondary amyloidosis. AA amyloidosis is a rare complication of inflammatory disease and chronic infection. AL amyloidosis, also known as primary amyloidosis, is caused by the deposition of abnormal immunoglobulin light chains, which can be identified on immunohistochemistry. AL amyloidosis is commonly associated with other plasma cell diseases, e.g. myeloma or Waldenström’s macroglobulinaemia.

Amyloid is deposited in the glomerular capillaries and mesangial cells and affects the ability of the kidney to filter and excrete waste and retain plasma protein. This leads to proteinuria and nephrotic syndrome. Approximately 20% of people with AL amyloidosis will progress to needing renal replacement therapy.

Histologically, the key feature of amyloidosis on light microscopy is eosinophilic deposits, which are seen in the mesangium. Congo Red staining is positive, giving the amyloid proteins a pink colour. Under polarised light, the tissue shows an apple-green birefringence. Renal biopsy is necessary in all suspected cases of renal amyloidosis.

Treatments are targeted at reducing the production of the amyloidogenic protein and this improves kidney function. High doses of melphalan (which is a chemotherapy agent) followed by stem cell transplantation are recommended for the treatment of AL amyloidosis. In AA amyloid, management involves control of the underlying condition; biologic therapies targeted against TNF-alpha, such as infliximab and etanercept can be used.