Abstract: PUB134
Rare Concurrent IgAN and Primary FSGS in a Solitary Kidney: A Proliferation-Inducing Ligand Inhibition as a Unified Long-Term Management Strategy
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Krafft, Justin, St Louis Kidney Consultants, St Louis, Missouri, United States
- Obeidat, Mohammad, Arkana Laboratories, Little Rock, Arkansas, United States
- Reisinger, Nathaniel, St Louis Kidney Consultants, St Louis, Missouri, United States
Introduction
Concurrent IgA nephropathy (IgAN) and primary immune-mediated focal segmental glomerulosclerosis (FSGS) on a single biopsy is exceedingly rare, and pathologists may consider IgA deposition incidental in the absence of active glomerular lesions. Both diseases share upstream B-cell dysregulation driven by APRIL (A Proliferation-Inducing Ligand), suggesting a potential common therapeutic target. We present a case where multicomorbidity led to selection of sibeprenlimab, a conditionally approved anti-APRIL monoclonal antibody, as long-term monotherapy.
Case Description
A 68-year-old man with a solitary kidney presented with nephrotic syndrome (proteinuria 18 g/24 h & eGFR 34). Biopsy showed primary FSGS with severe foot process effacement, 35% interstitial fibrosis, and mesangial IgA deposits confirmed on antigen retrieval and electron microscopy without active glomerular lesions. A renal genetic panel was negative. Prednisone and rituximab reduced UPCR from 18 to 0.66 g/g, but steroids were tapered urgently due to steroid adverse effects. A concurrent diagnosis of hypertrophic obstructive cardiomyopathy contraindicated ARBs and endothelin receptor antagonists. Sibeprenlimab was initiated for unified long-term management.
Discussion
APRIL drives pathogenic Gd-IgA1 production in IgAN, and emerging evidence implicates APRIL signaling in podocyte injury in FSGS. Sibeprenlimab reduced proteinuria by approximately 50% at 40 weeks in IgAN with a favorable safety profile. The PIONEER basket trial is actively investigating atacicept, a dual BAFF/APRIL inhibitor, in immune-mediated FSGS. This case supports APRIL inhibition as a rational, safe unified strategy for concurrent glomerular disease when conventional options are exhausted.
A. Toluidine blue: segmental sclerosis with endocapillary foam cells
B. Antigen-retrieved paraffin IgA stain: segmental granular mesangial staining
C-E. Diffuse foot process effacement & mesangial electron-dense deposits