Abstract: FR-PO0749
Necrotizing Crescentic Glomerulonephritis in COL4A3-Associated Alport Syndrome: Dual Pathology or Novel Phenotype?
Session Information
- Glomerular Diseases: ANCA Vasculitis, Anti-GBM Disease, and Crescentic GN
October 23, 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
- Gonuguntla, Samhitha, University of Iowa Health Care, Iowa City, Iowa, United States
- Jenigiri, Sreedevi Koppisetti, University of Iowa Health Care, Iowa City, Iowa, United States
Introduction
Alport syndrome is a hereditary nephropathy caused by pathogenic variants in COL4A3, COL4A4, or COL4A5, leading to abnormal type IV collagen within the glomerular basement membrane. Crescentic glomerulonephritis is rarely reported in native-kidney Alport syndrome and is typically described as non-necrotizing and non-inflammatory. In contrast, crescentic rapidly progressive glomerulonephritis (RPGN) is a clinical-pathologic syndrome characterized by rapid decline in renal function over days to weeks and histologically by necrotizing crescentic glomerulonephritis. Crescentic GN is classified into anti-GBM, immune-complex, and pauci-immune subtypes.
Case Description
A 27-year-old woman with hypertension and polycystic ovarian syndrome presented with rapidly worsening kidney function. Serologic evaluation for glomerulonephritis was negative except for a mildly elevated C4 level. The initial kidney biopsy revealed crescentic glomerulonephritis. A repeat biopsy was interpreted as pauci-immune crescentic GN. Despite treatment with glucocorticoids and rituximab, renal function continued to decline. Pathology re-review identified Alport syndrome with focal crescentic and sclerosing glomerulonephritis. Genetic testing detected a pathogenic COL4A3 c.3337+1G>A variant and a variant of uncertain significance, c.4421T>C (p.Leu147Pro). The patient was subsequently treated with glucocorticoids, rituximab, and avacopan.
Discussion
Crescents reported in Alport syndrome are generally considered non-inflammatory lesions related to glomerular basement membrane fragility and plasma leakage into the Bowman space. In contrast, the necrotizing lesions seen in this case resemble inflammatory rapidly progressive glomerulonephritis. This finding suggests either dual pathology with superimposed pauci-immune crescentic GN or a previously unrecognized inflammatory phenotype of COL4A3-associated disease. The pathogenic COL4A3 c.3337+1G>A splice-site variant provides strong evidence for underlying hereditary basement membrane disease, as canonical donor splice-site mutations typically result in abnormal collagen IV alpha-3 chain synthesis and are associated with more severe renal phenotypes. Persistent renal decline despite aggressive immunosuppression further complicates management. This case underscores the importance of genetic testing and pathology re-review in atypical crescentic GN presentations.