Identification of Factors Influencing Donor-Derived Cell-Free DNA Levels up to One Year After Kidney Transplant

Abstract

Introduction: Donor-derived cell-free DNA (dd-cfDNA) in the peripheral blood of allograft recipients has shown to early identify allograft injury. In this study, we assessed the factors that influence the amount of circulating dd-cfDNA during the first month postkidney transplant as well as its longitudinal trend. Materials and Methods: A consecutive series of 98 adult kidney transplant recipients at a single center between July 2018 and January 2020 were included in this study. All demographic and operative details were collected for donors and recipients of the organ transplant. Median eGFR, dd-cfDNA, and serum creatinine were calculated at 1, 2, 3, 6, and 12 month posttransplant. Descriptive statistics were used for patient demographics. Nonparametric comparisons of dd-cfDNA cumulative distributions between dichotomized groupings were evaluated using Kruskal-Wallis or Mann-Whitney U tests. Results: The median age of recipients was 54.5 years (IQR: 42.7-62.2). The cause of ESRD among recipients was hypertension (43%) and Type II diabetes mellitus (29%). Eighty-two percentage of patients received a deceased donor allograft, 14% received a living unrelated allograft, and 4% received a living related allograft. Sixteen percentage of recipients experienced delayed graft function (DGF). Median creatinine level at 1 month posttransplant was 1.75 mg/dL (IQR: 1.34-2.26) and median eGFR at 1 month posttransplant was 49.6 mL/min/1.73 m² (IQR: 35-65). The median dd-cfDNA score at 1 month posttransplant for all recipients was 0.4% (IQR: 0.15-5.3). Donor sex was a statistically significant differential for dd-cfDNA score. Recipients from male donors had a significantly higher median dd-cf DNA score at 1 month posttransplant versus those who received a female kidney (0.57% vs. 0.28%, p < 0.01). Highest median score was recorded at the first month posttransplant (0.4%, IQR: 0.26-0.74), and a sustained downward trend was observed through Month 2 (0.19%, IQR: 0.17-0.31) and Month 3 (0.19%, IQR: 0.15-0.26). Correlation between 1-, 2-, 3-, 6-, and 12-month posttransplant median dd-cfDNA scores between deceased donor and living donor (LRD and LURD) cohorts was not statistically significant. Conclusion: This study provides further insight into donor and recipient variables' effects on dd-cfDNA in the early posttransplant phase by analyzing a more diverse cohort of patients and adds to the knowledge around interpreting dd-cfDNA scores with clinical correlation for posttransplant management.

Figure 1

Effects of recipient demographics on median dd-cfDNA level 1 month posttransplant. (a) Cause of ESRD and median dd-cfDNA score at 1 month posttransplant. (b) HLA mismatch and median dd-cfDNA score at 1 month posttransplant. (c) Recipient ethnicity and median dd-cfDNA score at 1 month posttransplant. (d) Recipient sex and median dd-cfDNA score at 1 month posttransplant. (e) DGF status and median dd-cfDNA score at 1 month posttransplant.

Figure 2

Effects of donor demographics on median dd-cfDNA level 1 month posttransplant. (a) Donor sex and median dd-cfDNA score at 1 month posttransplant. (b) Donor/recipient combination and median dd-cfDNA score at 1 month posttransplant. FD/FR = female donor to female recipient, FD/MR = female donor to male recipient, MD/FR = male donor to female recipient, MD/MR = male donor to male recipient. (c) Living vs. deceased donor transplant. LRD = living related donor, LURD = living unrelated donor. (d) Donation after cardiac death (DCD) vs. donation after brain death (DBD).

Figure 3

Median dd-cfDNA score first 3 months posttransplant.

Figure 4

Longitudinal dd-cfDNA for Month 1, 2, 3, 6, and 12 posttransplant with transplant type.