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De Novo Membranous Nephropathy Associated with Antibody-mediated Rejection in Renal Transplant Recipients

M. V. Sousa1, L. G. Fernandes2, L. L. de Freitas3, R. L. Zollner2, M. Mazzali1

1Internal Medicine - Division of Nephrology, University of Campinas, Campinas, Brazil, 2Internal Medicine, University of Campinas, Campinas, Brazil, 3Pathology, University of Campinas, Campinas, Brazil

Meeting: 2021 American Transplant Congress

Abstract number: 1039

Keywords: Glomerulonephritis, HLA antibodies, Proteinuria, Rejection

Topic: Clinical Science » Kidney » Kidney Acute Antibody Mediated Rejection

Session Information

Session Name: Kidney Acute Antibody Mediated Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Membranous nephropathy (MN) is a rare autoimmune disease, with the potential to develop a persistent nephrotic syndrome and end-stage chronic renal disease in some patients, with a recurrence rate after transplant ranging from 30 to 40%. We report a case series of four kidney transplant recipients with biopsy-proven antibody-mediated rejection associated to histological findings compatible with membranous nephropathy. We reviewed the published literature on de novo MN associated with AMR and its treatment.

*Methods: Single-center retrospective cohort of kidney transplant recipients with donor-specific anti-HLA antibodies and biopsy-proven antibody-mediated rejection, with histological findings compatible with membranous nephropathy. We performed a literature review through a PubMed search using the terms “membranous nephropathy”, “antibody-mediated rejection”, “DSA”, “anti-HLA antibodies”. We selected case reports, systematic reviews, clinical trials, multicenter studies, and meta-analysis with cases of membranous nephropathy associated to antibody-mediated rejection.

*Results: The time post-transplant to this occurrence varied from 10 to 92 months. Two cases developed class II de novo anti-DQ DSA, and the others presented class I DSA. The patients with longer kidney transplantation presented more intense microvascular inflammation and histological findings of chronic injury, possibly due to subclinical immunological injury. In all these cases, we observed typical histological characteristics of membranous nephropathy, with subepithelial deposits with spikes. One patient did not receive AMR treatment due to infectious events. In other cases, it was administered intravenous immunoglobulin 2g/kg. Only one patient that developed class I DSA received plasmapheresis treatment. We observed one death due to infectious events and one graft failure in our sample. The other two patients remain with functioning grafts and using antiproteinuric drugs. DSA remains detectable in these cases, with routine solid-phase DSA test control every six months.

*Conclusions: Different from primary MN, where anti-PLA2R and IgG4 are usually detected, de novo MN might represent a form of immune response triggered by exposure of hidden antigens, probably different from those antigens observed in idiopathic MN, and IgG1 staining seems to be dominant. In the reported case, we observed de novo anti-DQ antibodies and C4d deposits in the graft. Probably, these antigens elicited immune response, which can lead to damage of podocytes and release of cytoplasmic- or membrane-associated podocytes proteins, with production of antibodies and immunocomplex and its deposition in the subepithelial area.

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To cite this abstract in AMA style:

Sousa MV, Fernandes LG, Freitas LLde, Zollner RL, Mazzali M. De Novo Membranous Nephropathy Associated with Antibody-mediated Rejection in Renal Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/de-novo-membranous-nephropathy-associated-with-antibody-mediated-rejection-in-renal-transplant-recipients/. Accessed May 11, 2025.

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