Elevated dd-cfDNA Levels to Monitor Patients with Delayed Graft Function

American Society of Transplant Surgeons Winter Symposium

Among recipients of deceased donor kidney transplants, approximately 31% are affected by delayed graft function; in 2% of those cases, delayed graft function remains unsolved beyond 2 weeks. Biomarkers that predict the time to resolution of delayed graft function would allow optimal immunosuppression levels in the period immediately post-transplant.

Noninvasive assessment of kidney allograft injury and rejection can be achieved via measurement of donor-derived cell-free DNA (dd-cfDNA). Patients with dd-cfDNA levels elevated ≥1% are at risk for kidney rejection.

There are few data on the ability of dd-cfDNA to predict resolution in delayed graft function. Obi Davies-Ekwenna, MD, of the University of Toledo Medical Center, Toledo, Ohio, and colleagues conducted a retrospective analysis of data on 16 patients who underwent deceased-donor kidney transplantation and subsequently developed delayed graft function. 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 Elevated Donor-Derived Cell-Free DNA in Patients with Delayed Graft Function.

At an average of 2 weeks post-transplant, Prospera,™ a clinically validated dd-cfDNA assay was used to detect active rejection in each patient. At 4 to 9 weeks post-transplant, 13 of the 16 patients had one or more follow-up blood draws. Seven of the 16 had a biopsy accompanying one of the dd-cfDNA tests.

Mean dd-cfDNA level at the first blood draw was 1.32% (range 0.03% to 4.98%). Average time from transplant to first test was 15.57 days (range 5 to 28 days). Seven of the 16 patients had for-cause biopsies, and two had rejection. Both patients who had rejection had initial dd-cfDNA readings ≥1% threshold.

At the time of the first blood draw, nine patients had elevated dd-cfDNA levels (≥1%). Six of seven patients whose dd-cfDNA levels were <1% had resolution of delayed graft function within 2 weeks. Of the nine patients with elevated dd-cfDNA levels, six had resolution of delayed graft function within 2 weeks. One patient who had consistently elevated dd-cfDNA levels had persistent delayed graft function. At the follow-up blood draw, there was a mean decline of 30% in dd-cfDNA levels among those with elevated levels at the first draw.

“in this cohort, dd-cfDNA readings <1% were consistent with resolution of delayed graft function. Persistently elevated dd-cfDNA levels were associated with delayed graft function. Serial dd-cfDNA testing can be beneficial in monitoring kidney transplant patients with delayed graft function,” the researchers said.

Source: Davies-Ekwenna O, Brown ML, McCormick S, et al. Elevated donor-derived cell-free DNA in patients with delayed graft function. Poster presented at the American Society of Transplant Surgeons virtual 21^st Annual State of the Art Winter Symposium (E-poster 50), January 14, 2021. Support for this study was provided by Natera, Inc.