UP FRONT MATTERS: Pathophysiology of the Renal BiopsyNephrotic Syndrome Due to an Amyloidogenic Mutation in Fibrinogen A α ChainPicken, Maria M.*; Linke, Reinhold P.† Author Information *Department of Pathology, Loyola University Medical Center, Maywood, Illinois; and †Reference Center of Amyloid Diseases, Martinsried, Germany Correspondence: Dr. Maria M. Picken, Department of Pathology, Building 110, Room 2242, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153. Phone: 708-327-2607; Fax: 708-327-2620; E-mail: [email protected], [email protected] Journal of the American Society of Nephrology 20(8):p 1681-1685, August 2009. | DOI: 10.1681/ASN.2008070813 Buy Metrics Abstract We identified amyloid derived from a mutant fibrinogen A α chain associated with one of the hereditary amyloidoses by kidney biopsy. The recognition of molecular and etiologic diversity among amyloidoses has revolutionized the management of systemic amyloidosis and necessitates precision in amyloid typing. Pitfalls and recommendations for the differential diagnosis of renal amyloid and current standards of amyloid typing are briefly discussed. Diagnosis of the amyloidosis type must be based on identification of the chemical composition of the amyloid protein in deposits and not on clinical suspicion, laboratory tests, or genetic testing. A clinical correlation is required to support but not make a diagnosis of amyloid type. If a hereditary form is detected by amyloid protein typing, then molecular studies are indicated. Conversely, in cases in which DNA sequence indicates a mutant amyloid precursor protein, protein analysis of the deposits must provide the definitive evidence. Negative or inconclusive results must be investigated further by a reference laboratory with the capability of applying more sophisticated methods. Copyright © 2009 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.