Abstract: TH-PO0083
Collapsing FSGS, APOL1, and Thrombotic Thrombocytopenic Purpura: Interplay Between Primary, Secondary, and/or Genetic Factors
Session Information
- AKI: Pathogenesis and Disease Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Yen, Timothy E., The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Atari, Mohammad, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Syed, Bushra, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Velagapudi, Ramya Krishna, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Tio, Maria Clarissa, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Obi, Yoshitsugu, The University of Mississippi Medical Center, Jackson, Mississippi, United States
- Dossabhoy, Neville R., The University of Mississippi Medical Center, Jackson, Mississippi, United States
Introduction
Focal Segmental Glomerular Sclerosis (FSGS) is associated with nephrotic syndrome (NS) and progression of kidney disease. FSGS can be classified broadly as having primary, secondary, genetic, or idiopathic etiologies.
Case Description
A 28-year-old Black, G5P3 female with hypertension and obesity presented with lower extremity edema ten days after a miscarriage. She was found to have an acute right leg DVT and AKI (sCr 1.5 mg/dL; baseline 0.7) associated with NS (sAlb 2.5 g/dL & UPCR 8.7 g/g). Autoimmune, hematologic, and viral serologic workups were negative. Renal biopsy was delayed by multiple factors including another miscarriage. Eight months after the initial presentation, UPCR was 15.3 g/g and sAlb was 1.3 g/dL. A renal biopsy was then performed and revealed collapsing FSGS as well as acute and chronic interstitial nephritis. Light microscopy showed ischemic changes and chronic endothelial injury on background of mild/moderate chronicity. Immunofluorescence was negative. Electron microscopy showed complete foot process effacement.
She started prednisone and tacrolimus for interstitial nephritis and possible primary podocytopathy. Isoniazid was added for latent TB. A comprehensive kidney gene panel (Renasight®) revealed homozygosity for APOL1 risk alleles and heterozygosity for an ADAMTS13 mutation associated with autosomal recessive familial thrombotic thrombocytopenic purpura (TTP). Despite lacking clinical features of TTP, she had low ADAMTS13 activity (0.21 IU/mL) above the diagnostic threshold (0.10 IU/mL) and inhibitor antibodies (1.4 BEU) suggesting a predisposition for both acquired and hereditary TTP.
NS persisted 4 months into treatment. Steroids were tapered and she received rituximab due to concern for subclinical TTP exacerbating FSGS and APOL1-mediated injury. After month 5, she remains on tacrolimus and low-dose prednisone. SCr has risen to 2.2-2.4 mg/dL with aggressive antiproteinuric therapy. She has achieved partial remission with resolution of edema, UPCR 5.3g/g, and sAlb 3.1 g/dL. ADAMTS13 activity is 0.4 IU/mL and inhibitor level is undetectable.
Discussion
The precise pathophysiology of this patient’s FSGS remains elusive and may involve the interplay of multiple secondary and genetic risk factors.