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Renal amyloidosis

INTRODUCTION

Amyloidosis is a group of diseases characterized by extracellular deposition of beta-sheet fibrils [1]. In the systemic forms, the amyloid causes progressive organ dysfunction leading to death of the patients. Over 20 proteins capable of amyloid formation have been identified. They include immunoglobulin (Ig) light chains in primary systemic amyloidosis (AL), Ig heavy chain (AH), amyloid A in secondary amyloidosis (AA), beta2-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 [2]. Another amyloidogenic protein is leukocyte chemotactic factor 2 (LECT2) [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) [1]. 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) [5]. This observation may be of diagnostic utility, since tissue amyloid deposits can be detected by scintigraphy following intravenous injection of radiolabeled SAP [5]. (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. The deposition of Ab2m occurs in patients on prolonged maintenance dialysis but may not affect the kidney [9]. (See "Dialysis-related amyloidosis".)

PATHOLOGY AND CLINICAL MANIFESTATIONS

Light microscopy — Light microscopy in renal amyloidosis typically reveals diffuse glomerular deposition of amorphous hyaline material, initially in the mesangium and then in the capillary loops (picture 1A-D). These nodules stain weakly with periodic acid Schiff's (PAS) and methenamine silver stain because they are composed mostly of amyloid fibrils and not extracellular matrix as in diabetes mellitus [9]. Scanty deposits of amyloid may go undetected by light microscopy. There is also a poor correlation between the extent of glomerular amyloid deposits and the degree of proteinuria.

            

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Literature review current through: Mar 2014. | This topic last updated: Sep 10, 2012.
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