Rare Coincidence or Secondary Process: Membranous Nephropathy with ANCA-Associated Vasculitis

Introduction: Membranous nephropathy (MN) is reported to occur in ANCA-associated vasculitis (AAV) and is usually thought of as secondary. We hereby contrast two cases with AAV both with membranous features one being PLA2R positive suggesting a primary disease process. Case Description: Case 1: A 70-year-old man with hypertension and chronic sinusitis presented with worsening nasal symptoms, fatigue, poor appetite, and arthralgias. He had severe acute kidney injury requiring dialysis. He had positive C-ANCA/ PR3 antibodies with hematuria and nephrotic-range proteinuria on urinalysis. Kidney biopsy confirmed pauci-immune necrotizing crescentic glomerulonephritis but also showed prominent membranous nephropathy features. Serologic PLA2R testing was negative along with negative tissue PLA2R and Exostosin 1/2 staining. Patient was treated with pulse steroids, plasmapheresis, and oral cyclophosphamide and was able to be liberated from dialysis (Creatinine nadir: 1.2 mg/dL). Proteinuria also trended down from UPCR 7.9 to 3.9 g/g. Due to concern for relapse 3 months into treatment, he was switched over to Rituximab. Remission was achieved after 7 months. Now 2 years after starting rituximab, patient remains in remission (creatinine 1.17mg/dL, UPCR 0.3g/g). Case 2: A 68-year-old female with hypertension and type 2 diabetes presented with generalized edema. She was found to have hematuria, proteinuria, and AKI (creatinine 1.1 mg/dL, baseline 0.7mg/dL). Albumin was 0.9 g/dL with proteinuria of 5.1 g/day. P-ANCA/MPO was positive with kidney biopsy showing pauci-immune crescentic glomerulonephritis along with prominent membranous features. Serologic PLA2R was positive. Patients was treated with pulse steroids and rituximab with serologic and clinical remission within 8 weeks. 5 years after diagnosis patient remains in complete remission (creatinine: 0.68 mg/dL, no hematuria or proteinuria). Discussion: These cases highlight that MN can occur in the context of AAV. Whether the MN is secondary to AAV is not clear but the PLA2R positive case suggests a seperate primary disease. This patient’s presentation with a primarily florid nephrotic syndrome with a mild AKI also suggests that. Rituximab based therapy resulted in remission of both diseases in both cases.