Diagnosis, Pathogenesis, Treatment, and Prognosis of Hereditary Fibrinogen Aα-Chain Amyloidosis
- 1 February 2009
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 20 (2), 444-451
- https://doi.org/10.1681/asn.2008060614
Abstract
Mutations in the fibrinogen Aα-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen Aα-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0–12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease.Keywords
This publication has 33 references indexed in Scilit:
- Hereditary Fibrinogen a Alpha-Chain AmyloidosisPublished by Informa UK Limited ,2007
- Human plasma fibrinogen is synthesized in the liverBlood, 2006
- Hereditary amyloidosis in early childhood associated with a novel insertion-deletion (indel) in the fibrinogen Aα chain geneKidney International, 2005
- Immunoglobulin light chain amyloidosis and the kidneyKidney International, 2002
- Apolipoprotein AI and Transthyretin as Components of Amyloid Fibrils in a Kindred with apoAI Leu178His AmyloidosisThe American Journal of Pathology, 2000
- Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen α‐chain variant in an English familyQJM: An International Journal of Medicine, 2000
- A Novel Apolipoprotein A-1 Variant, Arg173Pro, Associated with Cardiac and Cutaneous AmyloidosisBiochemical and Biophysical Research Communications, 1999
- Hereditary Amyloid Cardiomyopathy Caused by a Variant Apolipoprotein A1The American Journal of Pathology, 1999
- Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-IKidney International, 1998
- Hereditary renal amyloidosis with a novel variant fibrinogen.JCI Insight, 1994