Abstract: FR-PO0140
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)-APOA1 Amyloidosis Revealed by Kidney Biopsy with Parallel Genomics Approach
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Warner, David M., University of Cincinnati Academic Health Center, Cincinnati, Ohio, United States
- Nysather, Jacob A., University of Cincinnati Academic Health Center, Cincinnati, Ohio, United States
Introduction
APOA1 amyloidosis is a rare cause of systemic amyloidosis and ADTKD with multiorgan involvement. We present a case of ADTKD-APOA1 amyloidosis diagnosed with parallel kidney biopsy and genetic testing.
Case Description
A 49yoF w/ psoriatic arthritis and Hashimoto thyroiditis was referred to nephrology for an increase in Cr from 1.2 to 1.7 mg/dL in the setting of dehydration and concomitant NSAID, thiazide, and ACE inhibitor use. Despite treatment, her Cr continued to increase to a peak of 2.7 mg/dL. UA showed minimal proteinuria and no hematuria. Evaluation for monoclonal gammopathy, autoimmune disease, and infection was unrevealing.
Next Generation Sequencing revealed a heterogenous p.Leu99Pro mutation. Kidney biopsy demonstrated medulla-predominant Congo red-positive amyloid deposition with peritubular accentuation (Figure 1a, 1b, and 1c). LC-TMS confirmed APOA1 amyloidosis. This diagnosis prompted a workup for multiorgan involvement which is suspected, as outlined in Table 1. The patient’s son was found to have A2 CKD and underwent genetic testing which was negative for the mutation.
Discussion
This case highlights the importance of performing kidney biopsies with a parallel genomic approach and presents a few teaching points:
1. In patients with unexplained kidney dysfunction and systemic features, the absence of proteinuria and negative monoclonal studies does not exclude amyloidosis.
2. Biopsy-confirmed amyloidosis with medullary predominance with peritubular accentuation, glomerular sparing, and ADTKD should prompt consideration of hereditary amyloidosis, including APOA1 amyloidosis.
3. APOA1 amyloidosis is a multisystemic process requiring a detailed review of systems and multidisciplinary collaboration.
4. Given the autosomal dominant inheritance pattern, genetic counseling and cascade family testing are important for early detection and surveillance.