Abstract: FR-OR52
The Characteristics of Concurrent Anti-Glomerular Basement Membrane Nephritis and Membranous Nephropathy
Session Information
- Kidney Pathology: From Classic Clinicopathologic Studies to Computational Pathology
November 03, 2023 | Location: Room 109, Pennsylvania Convention Center
Abstract Time: 04:39 PM - 04:48 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Bu, Lihong, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Said, Samar M., Olmsted County Medical Center, Rochester, Minnesota, United States
- Herrera Hernandez, Loren Paola, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Madden, Benjamin J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
- Kim, Youngki, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Concurrent anti-glomerular basement membrane (GBM) nephritis and membranous nephropathy (MN) is rare and has been previously addressed only in case reports and small series (≤12 patients). Its target antigen is unknown.
Methods
We studied the clinicopathologic characteristics and outcome of 28 patients with anti-GBM nephritis and MN diagnosed at a large nephropathology laboratory over a 23-year period. A pathologic diagnosis of anti-GBM nephritis was defined by the immunofluorescence finding of intense linear GBM staining for IgG, in the absence of (or much weaker) staining for albumin, and concurrent MN was defined by the presence of segmental or global subepithelial deposits by electron microscopy.
Results
These cases are among 449 (6.2%) anti-GBM nephritis and 5183 (0.5%) non-lupus MN. The patients were 57% male and a median age of 54 years (range 15-82) at diagnosis. Most (96%) patients presented with acute kidney injury with a median serum creatinine at biopsy of 7.8 mg/dL (range 1.2-24.0), proteinuria (median 3.5 g/day, range 0.4-11) and hematuria. Kidney biopsy showed classic (n=26) or atypical (n=2) anti-GBM nephritis. Most patients received immunosuppressive therapy. After a median follow up of 17 months, 11% had complete remission (including the 2 with atypical anti-GBM nephritis), 27% had persistent kidney dysfunction, 62% progressed to ESKD. The rate of progression to ESKD was 93% in those on dialysis at presentation. The dominant IgG subclass of granular staining was different from that of linear staining, a feature facilitating the recognition of granular staining and thus the diagnosis of concurrent MN, particularly when EM unavailable. Immunostains for PLA2R, THSD7A, NELL-1 and EXT2 was negative in all cases tested. Proteomic analysis (n=8) of glomeruli did not detect any of the known or novel target antigens.
Conclusion
Concurrent classic anti-GBM nephritis and MN has poor prognosis, particularly in patients requiring dialysis at presentation, while atypical anti-GBM nephritis and MN has a favorable outcome. It is not associated with any of the known MN antigens and no novel target antigen(s) detected by mass spectrometry, favoring that the MN target antigen is likely an exposed structural GBM antigen.