American Society of Transplant Surgeons Winter Symposium 2021
The current gold standard for diagnosis of allograft rejection is biopsy. However, access to biopsy services is limited in some areas. Donor-derived cell-free DNA (dd-cfDNA), a novel biomarker for monitoring transplant recipients for allograft rejection, provides an easily accessible tool for monitoring allograft health, and is particularly useful in locations where access to rapid biopsy results is difficult.
During a virtual poster session at the American Society of Transplant Surgeons 21st Annual State of the Art Winter Symposium, David Ono, MD, Hawaii Kidney Specialists, Honolulu, Hawaii, and colleagues reported on results from a retrospective analysis of data from four kidney allograft patients who underwent serial dd-cfDNA testing to monitor for graft rejection. The nephrologynephrology was titled Clinical Utility of Donor-Derived Cell-Free DNA Testing for Allograft Rejection in Patients with Limited Access to Biopsy.
The researchers examined levels of dd-cfDNA with patient blood draws by Natera (San Carlos, CA) using a single nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) methodology.
- Female, 67 years of age. Recipient of a living non-related donor kidney transplant in 2009. Donor-specific antibodies developed in the absence of humoral rejection and patient was initiated on intravenous immunoglobulin therapy. Results of serial testing between March and October 2020 revealed transient increases in dd-cfDNA above the 1% threshold. Patient continually monitored for persistent changes in dd-cfDNA.
- Male, 66 years of age. Recipient of a deceased donor kidney allograft in 2009. History of biopsy-proven antibody-mediated rejection, cytomegalovirus, viremia, and acute kidney injury. Results of serial testing between June and October 2020 showed persistently elevated dd-CFDNA levels, suggesting ongoing injury.
- Female, 31 years of age. Received a second kidney transplant in 2015. In 2016, had elevated levels of serum creatinine and a biopsy-confirmed Banff stage-1 B mixed rejection, necessitating anti-rejection treatment. Results of serial testing between June and December 2020 demonstrated consistently elevated dd-cfDNA levels.
- Female, 32 years of age. Recipient of a living, related donor kidney transplant in 2017. History of BK viremia required reduced mycophenolate mofetil dosing; patient was stable with negative donor-specific antibodies results. Results of serial testing between July and December 2020 revealed consistently elevated dd-cfDNA levels and a mild elevation in serum creatinine.
In conclusion, the researchers said, “dd-cfDNA test results for these kidney transplant recipients reflected patient histories of allograft injury and rejection. In these cases, dd-cfDNA testing was able to provide ongoing monitoring of allograft health. In locations with limited access to rapid biopsy reads, such as Hawaii, dd-cfDNA testing through serial draws can provide valuable information about allograft health and identify when a more in-depth investigation is required.”
Source: Ono D, Hayashi R, McCormick S, et al. Clinical utility of donor-derived cell-free DNA testing for allograft rejection in patients with limited access to biopsy. Poster presented at the American Society of Transplant Surgeons virtual 21st Annual State of the Art Winter Symposium (E-poster 139), January 14, 2021. Support for this study was provided by Natera, Inc.