Membranous nephropathy in patients with anti-myeloperoxidase antibody associated systemic vasculitis: a report of two cases

Aim: to describe the presentation of membranous nephropathy (MN) in patients with systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase (MPO).Methods: in this article we report the retrospective data of two patients with MPO-ANCA-positive microscopic polyangiitis (MPA) and biopsy proven MN. ANCA-associated vasculitis (AAV) was diagnosed in accordance with the 2012 Chapel Hill Consensus Conference definitions and the 2022 classification criteria for MPA. Kidney biopsy specimen processing included light and immunofluorescence microscopy.Results: in both cases, the patients were male, the age of disease onset was 59 years (Patient 1) and 49 years (Patient 2). In Patient 1, the disease manifested with the interstitial lung lesions and nephritic syndrome, which was controlled by the administration of rituximab and glucocorticoids (GC). However, later the patient developed nephrotic syndrome refractory to therapy with calcineurin inhibitors, followed by nephritic syndrome. Remission was induced by cyclophosphamide and subsequent maintenance therapy with rituximab. A renal biopsy performed before the recurrence of nephritic syndrome revealed a picture of MN without evidence of extracapillary glomerulonephritis (ECGN). Patient 2 developed nephrotic syndrome at the disease onset, followed by the rapidly progressive glomerulonephritis and interstitial lung lesions which developed after unsuccessful therapy with calcineurin inhibitors and GC. Kidney biopsy revealed the co-existence of MN and necrotizing ECGN. Incomplete remission of the disease in the second case was achieved by treatment with cyclophosphamide followed by rituximab. Both patients had antibodies to MPO-ANCA and no antibodies to phospholipase A2 receptor (PLA2R) in circulation. In both cases, immunosuppressive therapy was complicated by the occurrence of infections, which resulted in the lethal outcome in Patient 1.Conclusion: MPO-ANCA-associated MN is a rare variant of glomerular lesions in AAV, which may precede or develop simultaneously with the typical ECGN and manifest as a combination of nephrotic and nephritic syndrome and/or rapidly progressive glomerulonephritis.