Abstract: SA-PO0988
Immunologic Insights: Donor-Derived Cell-Free DNA Elevation Uncovers ANCA-Associated Vasculitis Recurrence, a Case Series
Session Information
- Transplantation: Clinical - Case Reports
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Akkina, Sanjeev, Loyola University Medical Center, Chicago, Illinois, United States
- Qazi, Yasir A., Providence St Joseph Hospital Orange, Orange, California, United States
- Ky, Trung Q., Natera, Inc., Austin, Texas, United States
- Severe, Bailey, Natera, Inc., Austin, Texas, United States
Introduction
Donor-derived cell-free DNA (dd-cfDNA) is a validated biomarker for rejection, but can also indicate other forms of injury. In the ProActive study (NCT04091984), 10.5% of non-rejecting patients with elevated dd-cfDNA showed a recurrence of pre-transplant kidney disease. We present two cases where dd-cfDNA elevations helped identify recurrence of ANCA vasculitis.
Case Description
Case 1:
A 63-year old female with ANCA-associated glomerulonephritis (GN) received a kidney transplant; her serum creatinine (SCr) was 1.8 mg/dL 4 months post-transplant. A kidney biopsy at T=5mo showed borderline TCMR and vascular changes suggestive of chronic thrombotic microangiopathy (TMA). dd-cfDNA was 0.11%, indicating a low-risk for rejection. After pulsing with steroids, SCr decreased to 1.23 mg/dL. At T=8mo, SCr increased to 1.7 mg/dL with proteinuria and dd-cfDNA rose to 4.64%, prompting another biopsy showing borderline TCMR and possible fibrosed crescents. ANCA was positive at 1:40 dilution. The patient was treated with steroids and dd-cfDNA dropped to 0.61%. Approximately a year later, SCr increased to 1.67 mg/dL with no proteinuria, and dd-cfDNA increased to 1.87%. Kidney biopsy showed borderline TCMR, extraglomerular vessels with inflammatory cell infiltrates, and evidence of crescentic GN. After pulsing with steroids again, dd-cfDNA had decreased to 0.23%.
Case 2:
A 72-year old female with ESRD secondary to hypertensive nephropathy was retransplanted, and experienced slow graft function. At T=5mo, dd-cfDNA spiked to 4.53%; two weeks later it was 1.81%. During this time, the patient also had severe sinusitis and required sinus surgery. At T=6mo dd-cfDNA spiked again to 3.58%, and a biopsy was negative for rejection, but was suggestive for recurrent primary podocytopathy. Despite negative DSA, dd-cfDNA remained above 1%, prompting another biopsy at T=15mo, which showed microvascular inflammation of unknown significance. An ANCA panel was positive for circulating antibodies (1:320 dilution) suggesting ANCA vasculitis as the cause of inflammation identified on biopsy.
Discussion
In both cases, despite mild increases in SCr and biopsies showing no to mild rejection, elevations in dd-cfDNA prompted providers to search for other causes of kidney injury, such as recurrence of native kidney disease.