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Kidney Week

Abstract: TH-PO0628

Hereditary Transthyretin Amyloidosis and Biallelic APOL1 Gene Mutations Causing FSGS

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits

Authors

  • Bijuli-Singh, Lloyd, Broward Health Medical Center, Fort Lauderdale, Florida, United States
  • Garcia Pineiro, Evelyn, Broward Health Medical Center, Fort Lauderdale, Florida, United States
  • Aviles, Cinthya C, Broward Health Medical Center, Fort Lauderdale, Florida, United States
  • Eftekhari, Parham, Broward Health Medical Center, Fort Lauderdale, Florida, United States
Introduction

Genetic mutations linked to kidney disease often show population-specific patterns. APOL1 gene variations, found in about 13% of individuals with African ancestry, are linked to faster CKD progression and a higher risk of FSGS (1). Another genetic condition, hereditary transthyretin amyloidosis (ATTR), results from mutations in the TTR gene and can lead to systemic amyloid deposition, affecting the heart and kidneys, often with earlier onset in affected individuals (2). We report a patient with FSGS and both APOL1 and TTR variants.

Case Description

73 y.o. female with PMHx CKD 3b, HTN, DMT2 with microalbuminuria, HLD, RA, diastolic dysfunction presented outpatient for CKD evaluation. Patient had a strong FHx of ESRD and CKD. Labs showed Cr 1.49, BUN 22, GRF 37, UA negative for RBC/blood, only +2 protein. Due to strong FHx, Natera Renasight kidney gene panel was obtained. Results were positive for heterozygous TTR and high risk biallelic G1 and G2 variants of APOL1. Kidney biopsy revealed secondary FSGS, amyloid stain negative, diabetic glomerulosclerosis, mild tubulointerstitial disease 20-30%. Hypertension regimen was adjusted and patient was referred to advanced heart failure specialist where she was found to have heart failure and treatment with goal directed medical therapy was initiated.

Discussion

Genetic testing is rapidly transforming the landscape of kidney disease diagnosis and management, shaping the future of personalized care. This case illustrates the value of genetic screening, particularly in populations at higher risk for hereditary kidney disease. Detecting high-risk variants, such as APOL1 and TTR, can help predict disease progression, guide treatment, and inform long-term care planning. Early detection of FSGS is associated with improved clinical outcomes, as timely intervention can slow disease progression and hence preserve renal function (3). Identifying these variants also has implications for family members who may benefit from early testing and intervention. APOL1 is associated with increased risk of CKD, while TTR mutations can lead to amyloidosis-related heart failure. New therapies for ATTR are most effective when started early, before significant organ damage occurs. Without timely recognition, these genetic conditions can progress to ESKD or heart failure, where treatment becomes more limited if not futile.

Digital Object Identifier (DOI)