ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO1160

Beyond the Usual Suspects: FAT1-Positive De Novo Membranous Nephropathy in a Kidney Transplant Recipient

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Jaradat, Raghad, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Arwani, Suneel, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Yunas, Samia, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Syed, Bushra, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Velagapudi, Ramya Krishna, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Vaitla, Pradeep, The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Atari, Mohammad, The University of Mississippi Medical Center, Jackson, Mississippi, United States
Introduction

Membranous nephropathy (MN) in kidney transplant recipients is most commonly due to recurrent disease; however, de novo MN is increasingly recognized and often associated with alloimmune injury. We present a case of FAT1-positive de novo MN with persistent donor-specific antibodies (DSA) and mixed rejection.

Case Description

A 35-year-old male with end-stage kidney disease secondary to hypertension underwent deceased donor kidney transplantation with excellent allograft function. Induction immunosuppression included antithymocyte globulin and steroids with maintenance tacrolimus, mycophenolate mofetil and prednisone.
Post transplant course was complicated by borderline T cell–mediated rejection which was treated with corticosteroids with recovery of allograft function.
Later, another biopsy was done due to worsening proteinuria and rising DSA titers. Biopsy revealed antibody-mediated rejection (AMR) with membranous features and negative C4d. PLA2R, THSD7A, and NELL-1 were negative. Further testing showed positive ANA (1:80) but negative anti-dsDNA, negative monoclonal studies, and negative viral work up. He received steroids, IVIG, and rituximab with improvement in proteinuria and resolution of DQA1 but persistent DSA against DQ2.
Course was further complicated later with non-oliguric AKI and subnephrotic proteinuria. DSA titers were rising again with newly emergent DSA against DQA1, DR7, and DRB3. Biopsy showed plasma cell–rich T cell–mediated rejection (Banff IB), suspicion for vascular rejection, concerns for AMR, and membranous pattern glomerulonephritis. Mass spectrometry performed and showed a profile consistent with Procadherin FAT1 confirming FAT1 associated membranous. He was treated with steroids, ATG, and IVIG with improvement in creatinine but not back to baseline.

Discussion

FAT1, a podocyte transmembrane protein, has recently emerged as a novel antigen in MN. In kidney transplantation, de novo MN is increasingly linked to alloimmune injury in the context of AMR and positives DSAs.
In this case, the persistent and rising DSA with rejection demonstrates a temporal association between alloimmune activity and the development of FAT1-associated MN, raising the possibility that the recipient developed intolerance to FAT1 antigen. Additionally, this case underscores the role of mass spectrometry in PLA2R-negative MN for antigen identification and disease characterization.