Hereditary fibrinogen a α-chain amyloidosis: Phenotypic characterization of a systemic disease and the role of liver transplantation

Arie J. Stangou, Nicholas R. Banner, Bruce M. Hendry, Mohamed Rela, Bernard Portmann, Julia Wendon, Mark Monaghan, Philip MacCarthy, Muriel Buxton-Thomas, Christopher J. Mathias, Juris J. Liepnieks, John O'Grady, Nigel D. Heaton, Merrill D. Benson

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Variants of fibrinogen A α-chain (AFib) cause the most common type of hereditary renal amyloidosis in Europe and, possibly, the United States as well. Variant fibrinogen is produced in the liver, and solitary renal allografts fail within 1 to 7 years with recurrent amyloidosis. We assessed 22 AFib patients for combined liver and kidney transplantation (LKT) and report the clinical features and outcome. Twenty-one had E526V and 1, the R554L variant. Coronary atherosclerosis was identified in 68% and systemic atheromatosis in 55%. Vascular atheroma excised at endarterectomy and endomyocardial biopsies contained purely variant fibrinogen amyloid. Half had autonomic neuropathy. Six of 9 patients who underwent LKT are alive (67%), with good allograft function and no amyloidosis at median 67 months (range, 33-155 months) of follow-up. Serial technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy in 2 cases of preemptive LKT demonstrated preserved native kidney residual function at 5 years. Four explanted livers were used successfully for domino transplantation. Fibrinogen amyloidosis is a systemic amyloid disease with visceral, vascular, cardiac, and neurologic involvement. LKT is curative; however, cardiovascular amyloidosis may preclude this option. Our data encourage evaluation of preemptive solitary liver transplantation early in the course of amyloid nephropathy to prevent hemodialysis and kidney transplantation.

Original languageEnglish (US)
Pages (from-to)2998-3007
Number of pages10
JournalBlood
Volume115
Issue number15
DOIs
StatePublished - Apr 15 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Stangou, A. J., Banner, N. R., Hendry, B. M., Rela, M., Portmann, B., Wendon, J., Monaghan, M., MacCarthy, P., Buxton-Thomas, M., Mathias, C. J., Liepnieks, J. J., O'Grady, J., Heaton, N. D., & Benson, M. D. (2010). Hereditary fibrinogen a α-chain amyloidosis: Phenotypic characterization of a systemic disease and the role of liver transplantation. Blood, 115(15), 2998-3007. https://doi.org/10.1182/blood-2009-06-223792