Abstract: TH-PO0512
Two Hits, One Kidney: Unveiling Alport Syndrome in Progressive IgAN
Session Information
- Glomerular Diseases: IgAN, IgA Vasculitis, and More
October 22, 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
- Ike, Joanne, Allegheny Health Network, Pittsburgh, Pennsylvania, United States
- Khalil, Patricia, Allegheny Health Network, Pittsburgh, Pennsylvania, United States
- Arora, Swati, Allegheny Health Network, Pittsburgh, Pennsylvania, United States
Introduction
IgA nephropathy (IgAN), the most common cause of primary glomerulonephritis, is defined by IgA mesangial deposition and presents with hematuria and proteinuria. These clinical features can overlap with Alport syndrome, an inherited type IV collagen disorder, complicating diagnosis. This case illustrates the diagnostic challenge of their coexistence.
Case Description
A 47-year-old female with Crohn’s and celiac disease presented with hematuria and proteinuria. A kidney biopsy in 2016 showed IgAN ( M1E0S1T2). Over 10 years, eGFR declined from 31 to 21 ml/min/1.73 m3, and proteinuria persisted, though less than 1 g/day. By 2025, a family history of hearing loss, proteinuria, and hematuria in her maternal relatives prompted genetic testing and revealed a heterozygous COL4A4 mutation consistent with Alport syndrome. Subsequent repeat kidney biopsy showed moderate fibrosis, IgA2+, M0E0S0T1C0, with electron microscopy showing an irregular glomerular basement membrane with 'Basket weaving' and 'Crumbs of Liapis', confirming the coexistence of Alport syndrome and IgAN.
Discussion
IgAN and Alport can present similarly and may coexist. This coexistence may stem from shared pathogenic COL4 variants, found in both Alport syndrome and some familial IgAN, which weaken the GBM and potentially promote IgA deposition or impaired clearance. Given differing therapeutic approaches for each condition and the emergence of novel IgA therapeutics, relying solely on a single diagnostic test risks missing important treatment opportunities. Identifying underlying Alport syndrome also carries important prognostic implications for patients’ families, enabling genetic counseling. Therefore, clinicians should maintain a high index of suspicion for Alport syndrome in patients with biopsy-proven IgAN, especially if CKD progresses out of proportion to histologic findings or with a family history of hematuria or hearing loss. This case also raises the question of whether patients with genetically confirmed Alport syndrome should be offered kidney biopsy to evaluate for concomitant IgAN. More research in this area could help guide management.
Reference: Li Y, Groopman EE, DAgati V, et al. Type IV Collagen Mutations in Familial IgA Nephropathy. Kidney Int Rep. 2020;5:1075-1078. doi:10.1016/j.ekir.2020.04.011