De Novo Membranous Nephropathy Associated With Antibody-Mediated Rejection in Kidney Transplant Recipients

Background. Membranous nephropathy (MN) is a rare autoimmune disease that can develop a persistent nephrotic syndrome and end-stage kidney disease, with a recurrence rate of 30% to 40% after kidney transplant. Methods. Retrospective case series of membranous nephropathy observed in a cohort of kid-ney transplant recipients with donor-specific anti-human leukocyte antigen antibodies and biopsy-proven antibody-mediated rejection (AMR). Results. We report 4 cases of membranous nephropathy associated with AMR. MN was diag-nosed 10 to 92 months posttransplant, associated with de novo donor-specific antibodies, specific to class I in 2 cases, and class II in another 2. All cases presented typical morphology of membra-nous nephropathy, with subepithelial deposits with spikes at electron microscopy. Immunostain-ing for immunoglobulin G4 was negative in all cases, and podocyte-expressed M-type phospholipase A2 receptor was detected in glomerular basement membrane of 3 cases. Biopsy specimens from patients with longer follow-up showed more intense microvascular inflammation and chronic injury markers, possibly because of subclinical immunologic injury. AMR therapy included immunoglobulin 2g/kg in 3 patients, isolated or associated with plasmapheresis. One patient was not treated because of an active disseminated infection. Two patients remain with functioning grafts and under antiproteinuric therapy. Two grafts were lost, 1 because of chronic failure and the other because of death secondary to infection. Despite treatment, donor-specific antibodies remain detectable in a 6-month follow-up. Conclusions. De novo MN is a rare manifestation associated with AMR in kidney transplant recipients. The occurrence of podocyte-expressed M-type phospholipase A2 receptor in de novo MN suggests antibody-mediated activation, despite the use of maintenance immunosuppression.