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Abstract: FR-OR140

Clinical Utilization of Donor-Derived Cell-Free DNA (AlloSure) for Monitoring Kidney Transplants: The Colorado Experience

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Wiseman, Alexander C., University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States
  • Cooper, James E., University of Colorado at Denver, Denver, Colorado, United States
  • Davis, Scott, University of Colorado, Denver, Colorado, United States
  • Grafals, Monica, University of Colorado, Denver, Colorado, United States
  • Stites, Erik, University of Colorado, Denver, Colorado, United States
Background

Cell-free DNA is released by cellular apoptosis or damage. Donor-derived cell-free DNA (dd-cfDNA) released from kidney allografts can be differentiated from recipient cfDNA and correlates with graft injury due to rejection. Dd-cf-DNA may be an effective biomarker for monitoring immunologic risk and damage in kidney transplants. We recently implemented dd-cfDNA surveillance in all eligible kidney transplant recipients within three years of transplant at our center. Here we present our early experience.

Methods

All eligible kidney transplant recipients within three years of transplant at our center were enrolled in the surveillance protocol. Blood samples for dd-cfDNA are collected at 1, 2, 3, 4, and 6months post-transplant and then quarterly for the first 3years. A dd-cfDNA proportion of >1.0% was considered positive based on published data. Management of positive results were left to clinical discretion. Patients also undergo surveillance biopsy at 3 months post-transplant per our institutional protocol.

Results

In the first four months of the protocol, 394 samples have been collected from 256 patients. The dd-cfDNA was negative (<1.0%) in 95.2% (n=375) of samples analyzed. Nineteen samples from 18 patients were positive (>1.0%) with 13 patients undergoing subsequent biopsy. Six biopsies (46.2%) were confirmed diagnosis of rejection (2 with clinical rejection, 4 with subclinical rejection). Seven biopsies were not diagnostic of rejection (3 with no pathologic abnormality, 1 with ATN, 1 with glomerular disease, 1 with moderate glomerulitis, 1 with borderline cellular rejection). Twelve patients have had dd-cfDNA monitoring (a total of 22 samples, all <1.0%) and 3-month surveillance biopsies. Biopsies demonstrated no pathologic abnormality in 11 of 12 surveillance biopsies (91.7%). One biopsy had moderate peritubular capillaritis, moderate glomerulitis, and negative staining for C4d. The patient has stable graft function and no DSA.

Conclusion

To our knowledge, this is the largest published series to date using dd-cfDNA to monitor immunologic risk in kidney transplant recipients. A positive dd-cfDNA (>1.0%) had a PPV of 46.2% for biopsy-proven acute rejection, and importantly, 4 out of 6 of these cases were subclinical. A negative dd-cfDNA (<1.0%) had a NPV of 91.7% on 3-month surveillance biopsies.

Funding

  • Commercial Support