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Abstract: FR-PO1200

Elevated Donor-Derived Cell-Free DNA in Recurrent Lupus Nephritis After Kidney Transplantation: A Case Report

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Naik, Ruchi Harshadrai, University of Illinois Chicago, Chicago, Illinois, United States
  • Dabbas, Walaa, University of Illinois Chicago, Chicago, Illinois, United States
  • Ansari, Sajid Q., University of Illinois Chicago, Chicago, Illinois, United States
  • Hajjiri, Zahraa, University of Illinois Chicago, Chicago, Illinois, United States
  • Gallon, Lorenzo G., University of Illinois Chicago, Chicago, Illinois, United States
  • Setty, Suman, University of Illinois Chicago, Chicago, Illinois, United States
  • Campara, Maya, University of Illinois Chicago, Chicago, Illinois, United States
  • Pierce, Dana, University of Illinois Chicago, Chicago, Illinois, United States
  • Valdepenas, Benito, University of Illinois Chicago, Chicago, Illinois, United States
  • Soriano, Christopher, Natera Inc, Austin, Texas, United States
  • Xie, Jing, Natera Inc, Austin, Texas, United States
Introduction

Recurrent lupus nephritis (RLN) after kidney transplant (KT) is increasingly recognized but often underdiagnosed due to preserved allograft function and nonspecific biomarkers. Donor-derived cell-free DNA (dd-cfDNA), a validated biomarker for allograft rejection, may also indicate non-rejection injury, although this role remains unclear. We present a case of early RLN in an en bloc KT recipient, characterized by persistent dd-cfDNA elevation in the absence of rejection.

Case Description

A 25-year-old Hispanic female with ESKD secondary to lupus nephritis underwent en bloc deceased donor KT. She was sensitized (PRA class I 46%, class II 20%) with weak preformed Class I donor-specific antibodies and received thymoglobulin induction. Maintenance immunosuppression (tacrolimus, mycophenolate mofetil, and prednisone) was later transitioned to a belatacept-based regimen due to slow graft function. Following transition, she achieved excellent graft function (baseline SCr: 0.7 mg/dl). Three months post-KT, dd-cfDNA was elevated and remained high (1.9 to 2.5%) despite stable allograft function (FIGURE). A biopsy showed no evidence of rejection, with findings attributed to the pediatric donor. She later developed progressive proteinuria and persistent microscopic hematuria. Biopsy at six-months revealed global glomerular and diffuse mesangial expansion with full house pattern of immunofluorescence reactivity in glomeruli, suggestive of RLN without rejection. Lupus serologies remained active, including low C3 levels, while dd-cfDNA levels remained elevated.

Discussion

This case illustrates early RLN in a KT recipient with preserved graft function and persistent dd-cfDNA elevations in the absence of rejection. While dd-cfDNA is a sensitive marker of allograft rejection, it may also reflect global graft injury, including glomerulonephritis, as demonstrated by this case. RLN should be considered in patients with elevated dd-cfDNA and autoimmune disease, with integration of clinical serological and histological data essential for accurate diagnosis and management.

Timeline of Elevated dd-cfDNA and RLN