Renal Outcomes in Hereditary Fibrinogen A Alpha-Chain Amyloidosis

Hereditary fibrinogen A alpha-chain (AFib) amyloidosis is characterized by progressive proteinuric chronic kidney disease (CKD) and early progression to end-stage renal disease (ESRD). A large series published in 2009 showed renal survival <5 years from diagnosis and renal transplant survival of <10 years. Since then, advances in diagnostic techniques and nephroprotective care have transformed both nephrology and amyloidosis. We evaluated contemporary diagnostic and renal outcomes in the largest cohort of patients with AFib amyloidosis to date.

A total of 194 patients with confirmed AFib amyloidosis who were followed at a large national center and diagnosed between 1993 and 2025 were included. Patients were stratified by the era of diagnosis, pre- or post-2009. Diagnostic approaches, renal outcomes, transplant outcomes, and patient survival were evaluated.

Median age at diagnosis was 60 years with mean estimated glomerular filtration rate (eGFR) of 37 ml/min per 1.73 m². Proteomics-based amyloid typing became the predominant diagnostic modality post-2009 (60.5%). 62.8% progressed to ESRD. The mean annual rate of eGFR decline was 6.7 ml/min per 1.73 m² in the pre-2009 era and 4.8 ml/min per 1.73 m² in the post-2009 era. Renal survival improved post-2009, particularly among patients with CKD stage IIIA or B at diagnosis. Median renal allograft survival improved from 7.7 years in the pre-2009 era to 15.5 years in the post-2009 era (P = 0.006) (hazard ratio [HR], 4.5 [95% confidence interval [CI], 1.2-22.6]). Overall patient survival did not differ significantly between eras (median, 12 years; P = 0.69, log-rank).

Renal and allograft survival have improved since 2009, likely reflecting advances in supportive nephrology care. Isolated kidney transplantation is associated with favorable long-term outcomes. Despite improvements in renal survival, overall survival remains unchanged, underscoring the need for effective amyloid-targeted therapies.