Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis.
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.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Surendra
S
Dasari
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Md Shahrier
MS
Amin
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Paul J
PJ
Kurtin
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Julie A
JA
Vrana
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Jason D
JD
Theis
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Karen L
KL
Grogg
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Mariam P
MP
Alexander
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Samih H
SH
Nasr
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Fernando C
FC
Fervenza
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Nelson
N
Leung
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: sethi.sanjeev@mayo.edu.
Sanjeev
S
Sethi
D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D001054:Apolipoproteins A / Q000378:metabolism* / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000378:metabolism / Q000648:ultrastructure; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007679:Kidney Medulla / Q000473:pathology; D061346:Laser Capture Microdissection; D008297:Male; D013058:Mass Spectrometry; D008854:Microscopy, Electron; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology* / Q000473:pathology
D000682:Amyloid; D001054:Apolipoproteins A; D001057:Apolipoproteins E; C022205:apolipoprotein A-IV; D003404:Creatinine
amyloid; apolipoprotein A-IV; laser microdissection; mass spectrometry; medulla