Impact of Donor Type, Cold Ischemia Time, and Induction Type on Baseline Donor-Derived Cell-Free DNA in Kidney Transplant Recipients

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Donor-derived-cell-free DNA (dd-cfDNA) predicts acute rejection sooner in renal allografts.^1-4 Baseline dd-cfDNA levels are <1% in 96% of kidney transplant recipients (KTRs).¹ This study evaluated the impact of donor type, cold ischemia time (CIT), and induction type on baseline dd-cfDNA values.

We identified KTRs between September 2017 and June 2020 at our center who had dd-cfDNA (AlloSure, CareDx, Brisbane, CA) levels at 8 weeks post-transplantation. Those with 8-week baseline dd-cfDNA levels <1.0% were included in the analysis. Impact of donor type [living, donation after brain death (DBD), donation after circulatory death (DCD)], CIT, and induction received (thymoglobulin or basiliximab) were analyzed with 8-week dd-cfDNA.

There were 111 patients in the analysis. Among the study group, 39 received kidneys from living donors, 55 from DBD, and 17 from DCD donors. The CIT was <12 and ≥12 hours in 63 and 46 patients, respectively, with data missing in two. Thymoglobulin and basiliximab were the induction agents in 101 and 10 patients, respectively. There were no significant differences in baseline dd-cfDNA values for living vs. DBD vs. DCD donor types [median (IQR): 0.26% (0.19-0.43) vs. 0.24% (0.18-0.36) vs. 0.21% (0.17-0.42), p=0.59], CIT <12 hours vs. ≥ 12 hours [0.23% (0.17-0.47) vs. 0.26% (0.19-0.40), p=0.68] or Thymoglobulin vs. basiliximab induction [0.25% (0.18-0.41) vs. 0.23% (0.19-0.40), p=0.66] [Figure 1].

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Figure 1:

Comparison of 8-week baseline dd-cfDNA (AlloSure) for (a) living vs. DCD vs. DBD donor kidney recipients; (b) CIT <12 hours vs. ≥12 hours; and (c) induction with thymoglobulin vs. basiliximab. DBD: Donation after brain death, DCD: Donation after circulatory death, CIT: Cold ischemia time, dd-cfDNA: Donor derived cell free DNA. Each dot in the figures represents individual dd-cfDNA values.

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Our analysis showed similar baseline dd-cfDNA levels between living and deceased donor KTRs, even though DBD and DCD kidneys are prone to higher levels of injury from ischemia-reperfusion and immunological mismatch.⁵ Despite the contribution of prolonged CIT towards allograft injury through ischemia-reperfusion, this did not appreciably impact dd-cfDNA levels. More robust suppression of early immunological injury from depleting induction with thymoglobulin did not impact baseline dd-cfDNA levels. The current analysis suggests that peri-transplant variables may have minimal impact on baseline dd-cfDNA levels.