Dynamics of Donor-Derived Cell-Free DNA at the Early Phase After Pediatric Kidney Transplantation: A Prospective Cohort Study

Weijian Nie; Xiaojun Su; Longshan Liu; Jun Li; Qian Fu; Xirui Li; Chenglin Wu; Jiali Wang; Ronghai Deng; E Chen; Shicong Yang; Shujuan Li; Huanxi Zhang; Changxi Wang

doi:10.3389/fmed.2021.814517

Dynamics of Donor-Derived Cell-Free DNA at the Early Phase After Pediatric Kidney Transplantation: A Prospective Cohort Study

Front Med (Lausanne). 2022 Jan 7:8:814517. doi: 10.3389/fmed.2021.814517. eCollection 2021.

Authors

Weijian Nie¹, Xiaojun Su¹, Longshan Liu^{1

2

3}, Jun Li¹, Qian Fu¹, Xirui Li¹, Chenglin Wu¹, Jiali Wang⁴, Ronghai Deng¹, E Chen¹, Shicong Yang⁵, Shujuan Li⁶, Huanxi Zhang¹, Changxi Wang^{1

2

3}

Affiliations

¹ Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology, Guangzhou, China.
³ Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
⁴ Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁶ Department of Cardiovascular Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Background: Donor-derived cell-free DNA (ddcfDNA) has been suggested as an indicator of allograft injury in adult and pediatric kidney transplantation (KTx). However, the dynamics of ddcfDNA in pediatric KTx have not been investigated. In addition, it has not been demonstrated whether donor-recipient (D/R) size mismatch affect ddcfDNA level. Methods: Pediatric KTx recipients with a single donor kidney were enrolled and followed up for 1 year. ddcfDNA, calculated as a fraction (%) in the recipient plasma, was examined longitudinally within 3 months post-transplant. D/R size mismatch degree was described as D/R height ratio. The 33rd percentile of D/R height ratio (0.70) was used as the cut-off to divide the patients into low donor-recipient height ratio group (<0.70) and high donor-recipient height ratio group (≥0.70). The dynamics of ddcfDNA were analyzed and the impact factors were explored. Stable ddcfDNA was defined as the first lowest ddcfDNA. ddcfDNA flare-up was defined as a remarkable elevation by a proportion of >30% from stable value with a peak value >1% during elevation. Results: Twenty-one clinically stable recipients were enrolled. The median D/R height ratio was 0.83 (0.62-0.88). It took a median of 8 days for ddcfDNA to drop from day 1 and reach a stable value of 0.67% (0.46-0.73%). Nevertheless, 61.5% patients presented ddcfDNA>1% at day 30. Besides, 81.0% (17/21) of patients experienced elevated ddcfDNA and 47.6% (10/21) met the standard of ddcfDNA flare-up. Donor-recipient height ratio was an independent risk factor for ddcfDNA flare-up (odds ratio = 0.469 per 0.1, 95% CI 0.237-0.925, p = 0.029) and low donor-recipient height ratio (<0.70) was found to increase the risk of flare-up occurrence (odds ratio = 15.00, 95% CI 1.342-167.638, p = 0.028). Conclusions: ddcfDNA rebounds in many stable pediatric KTx recipients without rejection. This may be induced by significant D/R size mismatch and may affect its diagnostic performance at the early phase after pediatric KTx in children.

Keywords: donor-derived cell-free DNA; donor-recipient size mismatch; dynamics; pediatric donor; pediatric kidney transplantation.