Association of Donor-Derived Cell-Free DNA and Peripheral Blood Mononuclear Cells (PBMC) Gene Expression Profile with Graft Function Early After Kidney Transplant

Background: Donor-derived cell-free DNA (dd-cfDNA) and PBMC gene expression profiling (GEP) are non-invasive biomarkers associated with antibody and cell-mediated rejections, and allograft injury. dd-cfDNA assay is widely used for rejection screening after 1-month post-kidney transplant. Its utility and kinetics have not been evaluated in early post-transplant period, particularly with delayed graft function (DGF). In this study we explored the time course of changes in these biomarkers in patients with DGF vs slow/immediate graft function and whether they were associated with DGF duration. Methods: We performed a single-center prospective cohort study of patients underwent kidney transplantation during 10/2022-7/2024. DGF was defined as requiring dialysis within one week of transplantation. Both dd-cfDNA (AlloSure) and GEP (AlloMap) were measured on days 0,1,2,3,7, and weekly up to day 42. Results: 35 patients were included in this analysis. 6 received living donor transplants. 11 patients were female and 16 African American. The majority of patients received Alemtuzumab (26) for induction; others received rATG (4) or Basiliximab (5). 15 patients experienced DGF. The time course of dd-cfDNA for both groups is summarized in the figure. The dd-cfDNA scores tended to be higher in DGF group in the first 3 days, however, there were no significant differences between the two groups. Baseline dd-cfDNA levels were achieved by 1-week in both groups. GEP scores were comparable between the two groups in all time points. 12 patients had biopsy, none with rejection. Conclusion: Our preliminary results suggest that dd-cfDNA and GEP are not associated with early graft function or injury. dd-cfDNA levels decline to baseline as early as 7-days posttransplant, supporting its potential utility for rejection screening beginning the 1st week post-transplant. Funding: Commercial Support - CareDx