Impact of Delayed Graft Function on Baseline Donor Derived Cell Free DNA in Kidney Transplant Recipients

Dear Editor,

Donor derived-cell free DNA (dd-cfDNA) is a serum biomarker useful for earlier prediction of acute rejection in kidney allografts.^1-4 Baseline dd-cfDNA levels are <1% in 96% of kidney transplant recipients (KTRs).¹ A dd-cfDNA level ≥ 1% suggests possible allograft injury, usually from acute rejection.² We aimed to evaluate how delayed graft function (DGF) impacts baseline dd-cfDNA levels in kidney transplant recipients (KTRs).

We identified patients who underwent deceased donor kidney transplantation at our center between April 2018 and June 2020, who had dd-cfDNA measured 4-12 weeks post-transplant. A dd-cfDNA value ≥1.0% prompted allograft biopsy. Patients with biopsy evidence of rejection were excluded from the analysis. Patients were divided into 2 groups based on the presence or absence of DGF, which was defined as the need for dialysis during the first post-transplant week. The 4-12 week average and week 8 dd-cfDNA values were compared between the DGF and no-DGF groups using a t-test.

There were 80 deceased donor KTRs in the analysis (DGF, n=23; no-DGF=57) with 189 dd-cfDNA levels, including 56 in DGF and 123 in no-DGF groups. Average 4–12-week baseline dd-cfDNA levels were similar between DGF and no-DGF groups (0.39±0.21 vs. 0.49±0.44, p=0.17). Similarly, there was no significant difference in 8-week baseline dd-cfDNA levels between the two groups (0.30±0.18 vs.0.43± 0.45, p=0.07).

Despite the possibility of higher levels of ongoing intra-graft inflammation associated with DGF in KTRs,⁵ we did not observe higher baseline dd-cfDNA levels in these patients compared to KTRs who did not experience DGF. Our findings indicate that the development of DGF following kidney transplantation does not adversely impact the reliability of dd-cfDNA as a biomarker in predicting allograft rejection.