Abstract: TH-PO0775
Atypical Anti-Glomerular Basement Membrane Nephritis: Expanding the Clinical Spectrum
Session Information
- Glomerular Case Reports: Membranous, PGN, GBM, and More
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Marayati, Naoum Fares, Children's Hospital of Philadelphia, Department of Nephrology, Philadelphia, Pennsylvania, United States
- Ize-Iyamu, Aisosa, Children's Hospital of Philadelphia, Department of Nephrology, Philadelphia, Pennsylvania, United States
- Finn, Laura S., The Children's Hospital of Philadelphia Department of Pathology and Laboratory Medicine, Philadelphia, Pennsylvania, United States
- Kwok, Jonas, Children's Hospital of Philadelphia, Department of Nephrology, Philadelphia, Pennsylvania, United States
- McAteer, John, Children's Hospital of Philadelphia, Department of Nephrology, Philadelphia, Pennsylvania, United States
Introduction
Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder marked by autoantibodies against a specific domain of type 4 collagen in the GBM. While diagnosis typically begins with serologic testing, kidney biopsy remains the gold standard. Linear IgG staining along the GBM by immunofluorescence (IF) is a hallmark. We present a pediatric patient with diffuse linear IgG lambda-restricted staining on renal biopsy, negative anti-GBM serologies, and atypical histopathology raising consideration for alternative diagnoses.
Case Description
A previously healthy 9-year-old girl presented with abdominal pain, bilateral nephromegaly, and elevated creatinine (Cr 8.89 mg/dL). Urinalysis revealed nephrotic-range proteinuria and hematuria (UPCR 13 g/g). She remained clinically stable with maintained electrolyte balance and did not require RRT. Autoimmune and infectious workups were negative. Initial biopsy showed mild acute interstitial nephritis on light microscopy, prompting empiric high-dose steroids. Repeat biopsy for adequacy revealed normocellular glomeruli with subtly thickened membranes, no crescents, interstitial foam cells, linear IgG lambda GBM staining by IF, and EM findings of irregular GBM thickening with a basket-weave pattern, podocyte effacement, and no immune complex–type deposits. PLEX was deferred due to negative anti-GBM titers, and oral cyclophosphamide led to marked improvement in kidney function (Cr 1.89 mg/dL at discharge), though UPCR remained elevated (22.7 g/g). Genetic testing was pursued to investigate underlying membrane defects.
Discussion
This case was initially approached through an anti-GBM disease lens based on linear IF staining and response to standard anti-GBM therapy. However, the clinical course and EM findings on repeat biopsy were not consistent with anti-GBM disease. While linear IgG deposition is characteristic of anti-GBM disease, it can also result from other structural GBM changes that increase IgG affinity. A follow-up biopsy is planned to assess GBM structure outside the acute inflammatory phase. Genetic testing found variants in genes IFT140 and LAMB2, associated with irregular anti-GBM. Although anti-GBM therapy was effective, the atypical pathology underscores persistent diagnostic uncertainty, and the varied etiologies of nephritic syndromes with linear IgG staining.