Kidney nontumor
Associated with systemic conditions
Amyloidosis

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 9 July 2018, last major update December 2014

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Amyloidosis kidney [title] pathology

Cite this page: Sangle, N. Amyloidosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyamyloidosis.html. Accessed July 22nd, 2018.
Definition / general
  • Group of conditions with extracellular deposition of fibrillar proteins having an antiparallel, beta-pleated sheet tertiary structure, leading to Congo Red staining and apple green birefringence under polarized light
  • Amyloid is composed of a fibrillary protein (types described below) and nonfibrillary glycoproteins (amyloid P component also called serum amyloid P [SAP], glycosaminoglycans and apolipoprotein E)
  • Serum amyloid P may contribute to stability of amyloid deposits; radioactive iodine labeled SAP is used in nuclear medicine studies to assess amyloid deposition
  • Irrespective of molecular composition, amyloid always has the same characteristic histologic and ultrastructural appearance
  • Amyloid is resistant to digestion, accumulates within tissue, interferes with function and destroys vital organs
Clinical features
  • Renal amyloidosis causes 5% of adult cases of nephrotic syndrome
  • Suggestive of renal amyloidosis (Chinese study): middle-age, nephrotic syndrome, weight loss, organ enlargement, monoclonal light chains in serum or urine (Clin Lab 2011;57:947)
  • Systemic or localized
  • Duodenal biopsy is sensitive for diagnosing amyloidosis in chronic kidney disease patients, and highly correlates with renal amyloidosi (Clin Nephrol 2012;77:114)
  • Can determine specific type based on immunohistochemistry / immunofluoresence; also laser microdissection and mass spectrometry (Kidney Int 2012;82:226)

    AL type:
  • Also called primary amyloidosis
  • Most common cause of renal amyloidosis in US
  • Due to plasma cell dyscrasias with systemic deposition of amyloid and mild increase in bone marrow plasma cells that are monoclonal
  • 20% have myeloma or other lymphoproliferative disorders
  • Deposits are more likely lambda (75%) light chains or fragments than kappa type, often from amino-terminal fragment of variable region of light chain
  • Either vascular-limited or diffuse patterns (Nephrol Dial Transplant 2012;27:1097)
  • 40% develop nephrotic syndrome
  • Urinary exosomes may be useful to identify patients with AL amyloidosis (PLoS One 2012;7:e38061)
  • Poor prognosis (Intern Med 2011;50:2511); patients may develop acute leukemia after alkylating agents, secondary malignancies after autologous transplantation

    AA type:
  • Also called secondary amyloidosis
  • Associated with chronic inflammatory conditions such as osteomyelitis, bronchiectasis, decubitus ulcers, Crohn's disease, rheumatoid arthritis, tuberculosis (Swiss Med Wkly 2012;142:w13580)
  • Main amyloid component is protein A, derived from proteolytic cleavage of serum amyloid A protein, an acute phase reactant
  • 90% have renal insufficiency or nephrotic syndrome at diagnosis
  • Renal function is associated with amount of amyloid deposition (Rheumatol Int 2012;32:3155)
  • Treatment: treat the underlying inflammatory condition

    Beta 2 microglobulin type:
  • Associated with long-term hemodialysis or peritoneal dialysis; also renal failure between treatments; increases with duration of dialysis
  • Amyloid protein composed of intact and modified beta 2 microglobulin, an integral part of HLA class I antigen complex, that is usually eliminated by the kidney
  • Amyloid deposits occur in blood vessel walls, perineural and periarterial tissue, bone, joint, skin, subcutaneous tissue, heart, GI and lungs
  • May cause carpal tunnel syndrome, joint disease and bone cysts



    AH type:
  • Due to heavy chains
  • Very rare (predominantly lambda)
Case reports
Gross images

Images hosted on other servers:

Pale amyloid deposits in enlarged kidney

Microscopic (histologic) description
  • Salmon orange amorphous, fluffy, extracellular deposits in mesangium and subendothelium that obliterate glomeruli
  • Also deposits in blood vessel walls, interstitium and around tubules
  • Also mast cells that lead to interstitial fibrosis in AA type (Mod Pathol 2000;13:1020 )
  • Proposed histopathologic classification system (Arch Pathol Lab Med 2010;134:532)
  • 10% of AL patients lack glomerular deposits
  • Glomerular cell proliferations are uncommon
Microscopic (histologic) images

Images hosted on PathOut servers:

Glomerulus (PAS)

Glomerulus (Silver stain)

Glomerulus (Trichrome stain)

Glomeruli and interstitium


Congo red stain with polarization

Congo red stain without polarization

Positive lambda light chain stain in glomerulus


Positive Thioflavin-T staining in glomerulus

Predominant intracapillary deposition (PAS)

Predominant intracapillary deposition (Silver stain)



Images hosted on other servers:

Various images


Patient with Amyloid AA due to hidradenitis suppurativa (H&E, PAS, Congo Red)

Patient with familial Mediterranean fever

Positive stains
  • Congo Red: causes apple-green birefringence on polarization microscopy; staining lost in AA amyloidosis if pretreated with potassium permanganate
  • Silver stain: may show spiking along glomerular capillary loops
  • PAS: weak staining
  • Thioflavin T: fluoresces; may be positive for anti-AA antibodies, light chain restriction
Electron microscopy description
  • 7.5 - 10 nm in diameter fibrils with randomly dispersed, non branching arrangement in mesangium and subendothelium
Electron microscopy images

Images hosted on PathOut servers:

Amyloid fibrils on EM

Differential diagnosis