Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis

Surendra Dasari, Md Shahrier Amin, Paul J. Kurtin, Julie A. Vrana, Jason D. Theis, Karen L. Grogg, Mariam P Alexander, Samih H. Nasr, Fernando Custodio Fervenza, Nelson Leung, Sanjeev M Sethi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis.

Original languageEnglish (US)
Pages (from-to)658-664
Number of pages7
JournalKidney International
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2016

Fingerprint

Amyloidosis
Mass Spectrometry
Kidney
Biopsy
Amyloidogenic Proteins
Amyloid Plaques
Chronic Renal Insufficiency
Microdissection
Paraproteinemias
Apolipoproteins E
Proteinuria
Amyloid
Fluorescent Antibody Technique
apolipoprotein A-IV
Immunoglobulins
Blood Proteins
Creatinine
Electron Microscopy
Lasers
Peptides

Keywords

  • amyloid
  • apolipoprotein A-IV
  • laser microdissection
  • mass spectrometry
  • medulla

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis. / Dasari, Surendra; Amin, Md Shahrier; Kurtin, Paul J.; Vrana, Julie A.; Theis, Jason D.; Grogg, Karen L.; Alexander, Mariam P; Nasr, Samih H.; Fervenza, Fernando Custodio; Leung, Nelson; Sethi, Sanjeev M.

In: Kidney International, Vol. 90, No. 3, 01.09.2016, p. 658-664.

Research output: Contribution to journalArticle

Dasari, Surendra ; Amin, Md Shahrier ; Kurtin, Paul J. ; Vrana, Julie A. ; Theis, Jason D. ; Grogg, Karen L. ; Alexander, Mariam P ; Nasr, Samih H. ; Fervenza, Fernando Custodio ; Leung, Nelson ; Sethi, Sanjeev M. / Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis. In: Kidney International. 2016 ; Vol. 90, No. 3. pp. 658-664.
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AU - Theis, Jason D.

AU - Grogg, Karen L.

AU - Alexander, Mariam P

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AU - Sethi, Sanjeev M

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AB - Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo–red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis.

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