Abstract: SA-PO1055
Early Detection of Microvascular Injury in Renal Allografts Utilizing Donor-Derived Cell-Free DNA (cfDNA)
Session Information
- Transplantation: Clinical - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Khan, Naseer, Medical City Dallas Hospital, Dallas, Texas, United States
- Ilahe, Amna, Medical City Dallas Hospital, Dallas, Texas, United States
- Agha, Irfan, Medical City Dallas Hospital, Dallas, Texas, United States
Group or Team Name
- Dallas Renal Group.
Background
Early detection of allograft injury is critical in improving long-term allograft outcomes. Standard tests of renal function are insensitive, while renal biopsies are invasive and expensive. cfDNA allows sensitive surveillance of allograft injury. We present a series of patients where we identified microvascular injury (MVI) without evidence of alloantibody (DSA or donor directed non-HLA Ab) or C4d on biopsy based on elevatyed cfDNA.
Methods
We followed universal surveillance with cfDNA at month 1, 2, 3, then quarterly till 24 months. A biopsy was triggered if the surveillance value of cfDNA was >1%.Isolated MVI was diagnosed if their glomerulitis (g)+ peritubular capillaritis (ptc) score of >2 and C4d was negative. There were no other histopathological indicators of AMAR or CMR or infection based on Banff 2017 criteria. DSA and non-HLA antibodies ( anti-AT1R, Anti-MICA) were negative.
Results
We followed 120 consequetive patients from 2/2022 till 2/2023. 5 patients with isolated MVI biopsied solely on elevated cfDNA signature. Their renal function was normal. C4d , DSA and non-HLA antibody panels were negative. None of these biopsies satisfied the Banff 2017 criteria for AMAR Patients were treated based on individual physician prerogative.Patients 1 & 2 received steroids only. Patients 3 ,4 & 5 received steroids as well as 5 sessions of Plasmapharesis and IVIG. All five patients maintained renal function and showed decreased allograft injury based on reduced cfDNA signature (Table 1).
Conclusion
1. Surveillance with cfDNA is an important tool to detect allograft injury.
2. Early detection of MVI by cfDNA provides an opportunity to treat it before allograft dysfunction becomes apparent
3. The exact nature of isolated MVI remains unclear. It can be postulated as an alloimmune response or allograft injury due to missing self class I antigens.
4.The exact treatment regimen remains unclear. In our series, there was stabilization in injury based on cfDNA signature by increasing immunosuppression.
Donor Derived Cell-free DNA Results in Patients with Micro-vascular Injury
| Patient ID | Baseline Allosure % | Pre-Biopsy Allosure % | Post treatment Allosure % |
| 1 | 0.31 | 1.8 | 0.95 |
| 2 | 0.18 | 1.7 | 0.41 |
| 3 | 0.79 | 7.6 | 0.5 |
| 4 | 2.9 | 6.6 | 3.0 |
| 5 | 3.9 | 5.4 | 1.8 |