Amyloidosis is a group of diseases characterized by extracellular deposition of beta-sheet fibrils . In the systemic forms, the amyloid causes progressive organ dysfunction, leading to death of the patients. Over 25 proteins capable of amyloid formation have been identified. They include immunoglobulin (Ig) light chains (AL) and Ig heavy chains (AH) in primary systemic amyloidosis, amyloid A in secondary amyloidosis (AA), beta-2 microglobulin in dialysis-associated arthropathy (Ab2M), and amyloid beta protein (Ab) in Alzheimer disease and Down syndrome. There are also hereditary forms that include transthyretin (ATTR), apolipoprotein A-I (AApoAI) and A-II (AApoAII), gelsolin (AGel), lysozyme (ALys), fibrinogen A alpha chain (AFib), and others . Leukocyte chemotactic factor 2 (LECT2) is an amyloidogenic protein for which the pathogenic mechanism is incompletely understood [3,4].
Amyloid fibrils can be identified in biopsy specimens both by their characteristic appearance on electron microscopy and by their ability to bind Congo red (leading to apple-green birefringence under polarized light) and thioflavine T (producing an intense yellow-green fluorescence) . They are randomly organized and are approximately 8 to 10 nanometers in diameter.
Amyloid fibrils also avidly bind a normal circulating protein of uncertain physiologic significance called serum amyloid P component (SAP) . This observation may be of diagnostic utility since tissue amyloid deposits can be detected by scintigraphy following intravenous injection of radiolabeled SAP . (See "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)", section on 'Serum amyloid P component scintigraphy'.)
Clinically evident renal involvement mainly occurs in AL or AA amyloidosis [1,6-9]. Renal involvement can also occur in some hereditary forms of amyloidosis, most commonly in AFib, AApoAI, AApoAII, ALys, and AGel, but it is rare in ATTR. The deposition of Ab2m occurs in patients on prolonged maintenance dialysis; deposition in the kidney has been reported in autopsies but has no clinical significance . (See "Dialysis-related amyloidosis".)
This topic provides an overview of renal amyloidosis. A broad overview of amyloidosis, including diagnostic studies to determine the underlying etiology once a diagnosis of amyloidosis is confirmed, is presented elsewhere. (See "Overview of amyloidosis".)