Incorporation of dd-cfDNA Testing in Clinical Practice

American Society of Transplant Surgeons Winter Symposium 2021

The treatment of choice for patients with end-stage kidney disease is kidney transplantation. Renal allograft failure occurs in 20% to 30% of kidney transplant recipients within 5 years. The current gold standard for diagnosing allograft rejection is biopsy, which is costly, invasive, and may be associated with post-procedural complications. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for renal allograft injury including rejection.

Researchers at Natera, Inc., San Carlos, California, led by Mark Fajardo, recently conducted a retrospective analysis on 1347 dd-cfDNA tests from 879 renal allograft recipients at 33 sites. Results of the analysis were reported during a virtual poster session at the American Society of Transplant Surgeons 21^st Annual State of the Art Winter Symposium in a poster titled Assessment of Donor-Derived Cell-Free DNA for Allograft Rejection in Kidney Transplant Patients and Its Incorporation into Clinical Practice.

Blood samples were collected as part of routine clinical care, and the quality assurance team at Natera obtained data on biopsy and clinical follow-up. Prospera,™ a single-nucleotide polymorphism-based massively multiplexed-PCR test was used to identify dd-cfDNA in the 879 patients.

Of the 879 patients, 28 defined as high risk (dd-cfDNA fraction ≥1%) had definite biopsy results within 2 weeks of dd-cfDNA rejection test. Active rejection was diagnosed in 18 of those 28 high risk patients. Six of 10 biopsies with non-rejection showed other pathologic changes.

Median dd-cfDNA was higher in patients with T-Cell-mediated rejection (TCMR) than in those with antibody-mediated rejection (ABMR). Time to dd-cfDNA was longer for patients with ABMR rejection than for patients with TCMR, mixed rejection, or non-rejection.

In conclusion, the researchers said, “Analysis of real-world data revealed dd-cfDNA testing provided a 64% rejection rate among biopsies ordered by physicians in patients with a positive dd-cfDNA test. Abnormal pathological findings were noted in six of 10 biopsies with non-rejection consistent with allograft injury. dd-cfDNA identified TCMR, ABMR, and mixed rejection types, and dd-cfDNA detected active rejection both within the first year following transplant as well as after 1 year. Widespread adoption of routine dd-cfDNA testing may lead to a more judicious use of allograft biopsies and may detect rejection at an earlier, more treatable stage. Clinical follow-up provides vital information that is used to monitor test performance, identifies areas for additional research and development, and supports patient monitoring by providing longitudinal trend analysis.”

Source: Fajardo M, McCormick S, Ahmed E, et al. Assessment of donor-derived cell-free DNA for allograft rejection in kidney transplant patients and its incorporation into clinical practice. Poster presented at the American Society of Transplant Surgeons virtual 21^st Annual State of the Art Winter Symposium (E-poster 52), January 14, 2021. Support for this study was provided by Natera, Inc.