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Abstract: TH-PO650

Fibrinogen A Alpha-Chain Amyloidosis: A Brazilian Reality

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Feitosa, Valkercyo Araújo, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
  • Watanabe, Elieser H., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
  • Dourado, Vivian Christine, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
  • Neves, Precil D., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
  • Onuchic, Luiz F., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
Background

Fibrinogen A α-chain amyloidosis (AFib amyloidosis) results from mutations in the fibrinogen A α-chain gene (FGA) and is the most common form of hereditary renal amyloidosis.

Methods

We characterized the natural history and long-term outcomes of AFibE545V amyloidosis in patients diagnosed by clinical presentation, renal biopsy and/or genetic testing at the University of São Paulo Medical Center from 2014 to 2022.

Results

A total of 47 patients from 15 unrelated families with AFib amyloidosis were diagnosed by genetic testing, all heterozygous for the p.E545V variant: 31 (66%) with clinical manifestation and 16 (34%) with no clinical manifestation. During the follow-up, 31 developed kidney disease at a mean age of 55.0±10.4 years. Clinical presentation consisted of proteinuria (67.7%), hypertension (84%), and kidney failure (39.3%). Nineteen (61.3%) patients progressed to end-stage kidney disease (ESKD) at a mean of 62.0±10.7 years, with a mean kidney survival of 45.5±38,7 months. The rate of estimated glomerular filtration rate (eGFR) decline was 8.45±6.41 mL/min/1.73m2/year. Multivariate analysis showed that eGFR <60 mL/min/1.73m2 at diagnosis was an independent risk fator for progression to ESKD (HR 5.45 [95% CI, 1.04-28.68]). 11.5% of the patients underwent chemotherapy treatment, even without evidence of plasma cell disorder. Only 9 (60%) of the unrelated probands had a family history of CKD or amyloidosis. Differences in penetrance rate were observed according to the age of the patients: 77.4% (>50 years) vs 22.6% (<50 years), p=0.028.

Conclusion

AFibE545V amyloidosis showed significantly variable penetrance according to age range. In patients with hypertension, proteinuria, and progressive renal impairment, one should consider this diagnosis to carry out targeted genetic testing for AFib, particularly for the p.E545V variant, especially in family members of identified cases. This procedure would avoid inappropriate treatment.

Funding

  • Government Support – Non-U.S.