22-22: Renal Amyloidosis

Amyloidosis is a relatively rare cause of nephrotic syndrome. It is caused by tissue deposition of an overproduced and abnormally-folded protein (amyloid). Several different proteins can form amyloid fibrils with renal deposition. Primary amyloidosis, or AL amyloidosis, is the most common form and is due to a plasma cell dyscrasia causing overproduction and deposition of monoclonal Ig light chains (see Chapter 13). Secondary amyloidosis, or AA amyloidosis, can rarely occur in chronic inflammatory disease such as rheumatoid arthritis, IBD, or chronic infection; in these cases, there is deposition of an acute phase reactant, serum amyloid A protein. Other less common forms of amyloidosis may also be encountered.

Proteinuria, decreased GFR, and nephrotic syndrome are presenting symptoms and signs of renal involvement in amyloidosis; evidence of other organ involvement, such as the heart, is common. Serum and urine protein electrophoresis should be done as screening tests; if a monoclonal spike is found on either, serum free light chains should be quantified and the kappa:lambda ratio assessed. Amyloid-affected kidneys are often larger than 10 cm. Pathologically, glomeruli are filled with amorphous deposits that show green birefringence with Congo red staining.

AL amyloidosis progresses to ESKD in an average of 2–3 years. Five-year overall survival is less than 20%, with worse prognosis in those with advanced cardiac involvement. Standard treatment is a combination of melphalan, corticosteroids, and the proteosome inhibitor bortezomib; addition of daratumumab shows promise. Melphalan and autologous stem cell transplantation are associated with a high (45%) mortality rate but can induce remission in 80% of survivors; however, few patients are eligible for this treatment. In AA amyloidosis, remission can occur if the underlying disease is successfully treated. Renal transplantation is an option.