Early Kinetics of Donor-Derived Cell-Free DNA After Transplantation Predicts Renal Graft Recovery and Long-Term Function.

BACKGROUND

Ischemia-reperfusion injury (IRI) upon transplantation is one of the most impactful events that the kidney graft suffers during its life. Its clinical manifestation in the recipient, Delayed Graft Function (DGF), has indeed serious prognostic consequences. However, the different definitions of DGF are subjected to physicians' choices and centers' policies and a more objective tool to quantify IRI is needed. Here, we propose the use of donor-derived cell-free DNA (ddcfDNA) for this scope.

METHODS

ddcfDNA was assessed in 61 kidney transplant recipients of either living or deceased donors at 24 hours, 7, 14 and 30 days after transplantation using the AlloSeq cfDNA Kit (CareDx, San Francisco, CA, US). Patients were followed-up for 6 months and 7-year graft survival was estimated through the complete and functional iBox tool.

RESULTS

24-hour ddcfDNA was associated with functional DGF (7.20[2.35-15.50]% in patients with fDGF versus 2.70[1.55-4.05]% in patients without it, P = 0.023) and 6-month eGFR (r = -0.311, P = 0.023). At day 7 after transplantation, ddcfDNA was associated with dialysis duration in DGF patients (r = 0.612, P = 0.005) and worse 7-year iBox-estimated graft survival probability (β-0.42, P = 0.001) at multivariable analysis. Patients with early normalization of ddcfDNA (<0.5% at 1 week) had improved functional iBox-estimated probability of graft survival (79.5 ± 16.8%) in comparison with patients with 7-day ddcfDNA ≥ 0.5% (67.7 ± 24.1%) (P = 0.047).

CONCLUSIONS

ddcfDNA early kinetics after transplantation reflects recovery from IRI and is associated with short-, medium- and long-term graft outcome. It may provide a more objective estimate of IRI severity in comparison with the clinical-based definitions of DGF.

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.