title: Clinical, biopsy, and mass spectrometry findings of renal gelsolin amyloidosis.
abstract: Gelsolin amyloidosis is a rare type of amyloidosis typically involving the cranial and peripheral nerves, but rarely the kidney. Here we report the clinical, kidney biopsy, and mass spectrometry findings in 12 cases of renal gelsolin amyloidosis. Of the 12 patients, five were men and seven were women with mean age at diagnosis of 63.8 years. Gelsolin amyloidosis was most common in Caucasians (six patients) and Asians (four patients), and included one each African-American and Hispanic patients. Nephrotic syndrome was the most common cause of biopsy, although most patients also had progressive loss of kidney function. Hematological and serological evaluation was negative in 11 patients, while one patient had a monoclonal gammopathy. The renal biopsy showed large amounts of pale eosinophilic Congo red-positive amyloid deposits typically restricted to the glomeruli. Immunofluorescence studies were negative for immunoglobulins in nine cases with three cases of smudgy glomerular staining for IgG. Electron microscopy showed mostly random arrangement of amyloid fibrils with focally parallel bundles/sheets of amyloid fibrils present. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra numbers for gelsolin, serum amyloid P component, and apolipoproteins E and AIV. Furthermore, the p. Asn211Lys gelsolin mutation on mass spectrometry studies was detected in three patients by mass spectrometry, which appears to represent a renal-limited form of gelsolin amyloidosis. Thus, renal gelsolin amyloidosis is seen in older patients, presents with nephrotic syndrome and progressive chronic kidney disease, and histologically exhibits glomerular involvement. The diagnosis can be confirmed by mass spectrometry studies.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: sethi.sanjeev@mayo.edu.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Md Shahrier
authors.initials: MS
authors.lastname: Amin
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Mariam P
authors.initials: MP
authors.lastname: Alexander
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001054:Apolipoproteins A / Q000032:analysis; D001057:Apolipoproteins E / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003317:Corneal Dystrophies, Hereditary / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018260:Gelsolin / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry* / Q000473:pathology* / Q000648:ultrastructure; D007674:Kidney Diseases / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000209:etiology; D011237:Predictive Value of Tests; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000209:etiology; D000683:Serum Amyloid P-Component / Q000032:analysis; D053719:Tandem Mass Spectrometry
chemical_list: C000612345:ApoE protein, human; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D015415:Biomarkers; D018260:Gelsolin; D000683:Serum Amyloid P-Component; C022205:apolipoprotein A-IV
keywords: amyloid; gelsolin; kidney; laser microdissection; mass spectrometry