RENAL PATHOLOGY LEARNING

Renal Amyloidosis (Part I)

by

Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Milan, Italy

 

The term amyloidosis refers to the deposition of an amorphous substance defined by the presence of a fibrillar structure by electron microscopy and a characteristic beta-pleated sheet structure by x-ray diffraction. The existence of this group of diseases has been known for centuries, but major advances in the elucidation of the nature of the deposits have been achieved in the past few years. It is now known that the beta-sheet configuration responsible for the general appearance of amyloid deposits is common to a large variety of proteins. This tertiary structure is responsible for the characteristic tinctorial and optical properties evident with Congo red staining. The material that accumulates in the extracellular compartment progressively destroys the involved organ.

The accumulation of amyloid deposits may complicate the course of various diseases. Classifications of amyloid disorders reflect some of the current concepts concerning the protein composition of amyloid fibrils in different diseases.

Classification of amyloidoses

Type

Precursor protein

Involved organs

Associated clinical syndrome

AL (AH)

Ig light chain (heavy chain)

Systemic (mostly kidneys, liver, heart, spleen, vessels, lungs, gastrointestinal tract, nerves, tongue)

Systemic amyloidosis (multiple organ involvement)

Rarely, localized amyloidosis (orbital, for instance)

A 2m

?2 -Microglobulin

Systemic (mostly musculo-skeletal system, heart, synovium)

Hemodialysis-associated amyloidosis

AA

SAA apolipoprotein

Systemic (mostly spleen, liver, kidneys)

Systemic secondary amyloidosis

Familial Mediterranean fever

AapoA1

Apolipoprotein A1

Nerves

Peripheral neuropathy

ATTR

Transthyretin

Nervous system, kidneys, thyroid, heart

Familial amyloid polyneuropathy

Senile systemic amyloidosis

AGel

Gelsolin

Systemic (vessels)

Finnish hereditary systemic

amyloidosis

A

-Amyloid precursor protein

Brain

Alzheimer's disease

Down's syndrome

APrP

Prion P

Brain

Creutzfeldt-Jakob disease and other spongiform encephalopathies

ACys

Cystatin C

Brain and other tissues

Iceland-type hereditary amyloid angiopathy

AIAPP

Islet amyloid polypeptide

Pancreas

Insulinoma, type II diabetes

ACal

Procalcitonin

Thyroid

Thyroid medullary carcinoma

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Renal biopsy is fundamental because the demonstration by histology of amyloid deposition is necessary and the tissue most frequently involved by amyloidosis is the kidney. Depending on peptide subunit deposition, the two most frequent types of amyloidosis have been defined, AL and AA, that can be differentiated using histochemistry and immuno-histochemistry techniques.

By light microscopy, amyloid appears as an amorphic, eosinophilic, PAS negative or scantly positive, extracellular substance.

Its deposition is present not only in glomeruli, but also in the wall of arteries and arterioles.

 

 

HISTOCHEMICAL STAININGS
Three histochemical stainings can be used for amyloid identification:
1. Crystal violet or methyl violet metachromatic staining
2. Thioflavin (T or S) fluorescent staining
3. Congo Red or Sirius Red direct staining

 

Crystal violet stains amyloid deposits, that are present in both glomeruli and vessels.

Glomeruli and vessels appear diffusely positive when stained with fluorescent Thioflavin T.

Congo Red positivity is the most reliable staining in diagnosing amyloid deposition.

 

When stained with Congo Red, the sections show a typical apple-green birefringence under polarized light. Loss of Congo Red staining caused by pretreatment of the tissue with potassium permanganate is a useful tool for the diagnosis of amyloidosis AA.

IMMUNOHISTOCHEMICAL STAININGS
To differentiate amyloid AL and AA, specific antibodies can also be used.
Anti-immunoglobulin light chains (k e l) are useful for amyloid AL diagnosis.

 

An antibody against the AA protein is now available. Amyloid AA positivity is evident in glomeruli, arteries, and arterioles.

Ultrastructural examination remains a fundamental tool for amyloid deposition diagnosis. Typically non branching irregular fibrils can be demonstrated.

 

Questions

 

Read all the Renal Pathology publications

REFERENCES
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2.

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Donini U, Casanova S, Zucchelli P, et al. Immunoelectron microscopic classification of amyloid in renal biopsies. J Histochem Cytochem 1989; 37: 1101-6.

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Merlini G, Anesi E, Garini P et al. Treatment of AL amyloidosis with 4'-Iodo-4'-deoxydoxorubicin: an update. Blood 1999; 93: 1112-3.

8.

Goldsmith DJA, Sandooran D, Short CD, et al. Twenty-one year survival with systemic AL-amyloidosis. Am J Med 1996; 28: 278-82.