Mutations in the fibrinogen A alpha-chain gene are the most common cause of 
hereditary renal amyloidosis in the United Kingdom. Previous reports of 
fibrinogen A alpha-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.