Amyloidosis is caused by tissue deposition of an abnormally folded protein (amyloid). Several different proteins can form amyloid fibrils. 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 13-37). Secondary amyloidosis, or AA amyloidosis, results from a chronic inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease, 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 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. 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 ESRD in an average of 2–3 years. Five-year overall survival is less than 20%, with death occurring from ESRD and heart disease. Standard treatment is a combination of melphalan, corticosteroids, and the proteosome inhibitor bortezomib. A greater than 90% reduction in the level of serum free light chains correlates with improved renal outcomes. Melphalan and 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 treated. Renal transplantation is an option.
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