A RARE CASE OF CONCURRENT ANTI-GLOMERULAR BASEMENT MEMBRANE NEPHRITIS AND MEMBRANOUS NEPHROPATHY WITH POSITIVE ANCA

Anti–glomerular basement membrane (GBM) nephritis is characterized by rapidly progressive glomerular injury and is associated with a high risk for progression to end-stage kidney disease. We report a rare case of concurrent anti-GBM nephritis and membranous nephropathy (MN) with positive serum antineutrophilic cytoplasmic autoantibodies (ANCA).

Case Presentation: A 58-year-old male without prior medical history was referred due to a 2-month history of fatigue, loss of appetite, weight loss of 5kg and low-grade fever. In the preceding weeks, he also developed oliguria. He had a 35-year history of smoking approximately 30 cigarettes per day. Urinalysis revealed marked hematuria and proteinuria (7.47 g/gCRE). Laboratory tests revealed elevated inflammatory markers (ESR, 114 mm/h; CRP, 16.52 mg/dL), hypoalbuminemia (2.8 g/dL), and advanced kidney impairment (BUN, 74.6 mg/dL; CRE, 15.03 mg/dL), with positive titer of anti-GBM antibody (570.7 U/mL) and myeloperoxidase (MPO)-ANCA (26.1 U/mL). Chest computed tomography excluded pulmonary hemorrhage and interstitial pneumonia. Hemodialysis was initiated three times per week after admission. Intravenous methylprednisolone pulse therapy (500mg/body x 3 days) , followed by oral prednisolone (1 mg/kg/day), was administered. Kidney biopsy demonstrated diffuse cellular and fibrocellular crescentic glomerulonephritis involving 24 of 29 glomeruli, with spike formations in residual glomeruli. No evidence of vasculitis was observed in the arterioles. Immunofluorescence analysis demonstrated both linear and granular deposition of IgG and C3 along the glomerular capillary walls, whereas staining for specific target antigens associated with primary and secondary membranous nephropathy, including M-type phospholipase A2 receptor (PLA2R), were negative. Electron microscope showed subepithelial electron-dense deposits. Based on these findings, a diagnosis of anti-GBM nephritis concurrent with MN was established. Following the addition of fourteen sessions of plasma exchange to the immunosuppressive therapy, the titer of anti-GBM antibody decreased to 4.8 U/mL; however, kidney function failed to recover, and the patient remained dialysis dependent.

Discussion: This patient presented with rapidly progressive glomerulonephritis and severe proteinuria. Kidney biopsy demonstrated crescentic anti-GBM glomerulonephritis with MN, based on both linear and granular deposition of IgG and C3 on immunofluorescence and subepithelial electron-dense deposits on electron microscopy. Identification of the specific target antigens (e.g., PLA2R, NELL1, THSD7A, EXT1/2) may confirm primary and secondary MN and assist in guiding appropriate therapeutic approaches. Furthermore, recent reports have shown that MPO immunostaining may be useful in diagnosing MN secondary to MPO-ANCA-associated vasculitis. In this case, we postulated that MN might have preceded and subsequently induced the formation of anti-GBM antibodies. However, these antigen stains were all negative. Nevertheless, these antigen-based analysis provide valuable insight into the underlying pathophysiology. The coexistence of anti–GBM nephritis and MN with MPO-ANCA positivity is exceptionally uncommon, and the clinical relevance of this association warrant further investigation. This work was first presented at ASN Kidney Week 2025, and re-submission is permitted by ASN.