Kidney Week

Abstract: SA-PO0781

Beyond Minimal Change: A Hidden Diagnosis of Hereditary Transthyretin Amyloidosis

Session Information

• Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Flores, Jackeline, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Jackeline Flores, MD

• Beltagy, Asmaa, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Asmaa Beltagy, MD, PhD

• Flowers, Addie, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Addie Flowers, MD

• Natarajan, Piruthiviraj, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Piruthiviraj Natarajan, MD

• Pena, Camilo, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Camilo Pena, MD, FASN

Introduction

Nephrotic syndrome in young adults is commonly attributed to primary glomerular diseases such as minimal change disease. However, resistance to immunosuppressive therapy should prompt evaluation for secondary causes. Hereditary transthyretin amyloidosis is a rare multisystem disorder that may rarely present with renal involvement.

Case Description

A 30-year-old female with presumed minimal change disease had persistent nephrotic syndrome despite treatment with corticosteroids, tacrolimus, and later rituximab. She experienced recurrent hospitalizations for volume overload and a repeat evaluation was pursued due to concerns for steroid resistance. Kidney biopsy review showed minimal interstitial fibrosis (<10%), no immune complex deposition, and partial foot process effacement, findings not consistent with a primary podocytopathy. Secondary causes were suspected, though focal segmental glomerulosclerosis could not be excluded.

Genetic testing was positive for Autosomal Dominant Amyloidosis (HATTR type) with TTR gene defect detected with a variant of c.424G>A (p.Val142Ile). Additional studies, including serum free light chains and electrophoresis, were obtained. Multidisciplinary evaluation supported this as a potential early systemic manifestation. She was counseled regarding the diagnosis and candidacy for disease-modifying therapy.

Discussion

Genetic testing is an important tool in atypical or treatment-resistant cases and may reveal systemic conditions requiring specialized management. This case underscores the importance of reconsidering diagnosis in refractory nephrotic syndrome. ATTR amyloidosis is a rare, inherited, progressive, and fatal disease caused by mutations in the TTR gene that leads to the buildup of abnormal amyloid proteins in nerves, heart, and other organs, resulting in neuropathy, cardiomyopathy, and organ dysfunction. An early recognition is critical, as targeted therapies can slow progression. The TTR gene defect noted in the patient detected the variant of c.424G>A (p.Val142Ile) that is associated with cardiac amyloidosis which presents as a late onset cardiomyopathy typically without kidney involvement or peripheral neuropathy. Renal involvement in p.Val142Ile carriers is uncommon and not a typical feature of this variant. Kidney disease in TTR amyloidosis is most strongly associated with the Val30Met variant, not Val142Ile highlighting the value of this case.