TY - JOUR
T1 - Utilization of donor-derived Cell-Free DNA in pediatric kidney transplant recipients
T2 - A single center study
AU - Ranch, Daniel
AU - Fei, Mingwei
AU - Kincade, Elisabeth
AU - Piburn, Kim
AU - Hitchman, Kelley
AU - Klein, Kelsey
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2024/2
Y1 - 2024/2
N2 - High donor-derived cell-free DNA (dd-cfDNA) levels indicate transplant allograft injury and can identify graft rejection in kidney transplant recipients. Here, we evaluated the use of dd-cfDNA in pediatric kidney transplant rejection monitoring and treatment. Methods: Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). Results: Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p =.0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34–3.12] vs. 0.24% [0.08–0.78], p <.0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27–1.8] vs. 0.26% [0.08–2], p =.0437). Median change in dd-cfDNA after rejection treatment was −0.57% (−1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0–19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p =.2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. Conclusions: Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.
AB - High donor-derived cell-free DNA (dd-cfDNA) levels indicate transplant allograft injury and can identify graft rejection in kidney transplant recipients. Here, we evaluated the use of dd-cfDNA in pediatric kidney transplant rejection monitoring and treatment. Methods: Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). Results: Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p =.0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34–3.12] vs. 0.24% [0.08–0.78], p <.0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27–1.8] vs. 0.26% [0.08–2], p =.0437). Median change in dd-cfDNA after rejection treatment was −0.57% (−1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0–19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p =.2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. Conclusions: Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.
KW - acute rejection
KW - anti-HLA antibody
KW - antibody mediated rejection
KW - pediatric kidney transplantation
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U2 - 10.1111/petr.14582
DO - 10.1111/petr.14582
M3 - Article
C2 - 37550268
AN - SCOPUS:85167331908
SN - 1397-3142
VL - 28
JO - Pediatric Transplantation
JF - Pediatric Transplantation
IS - 1
M1 - e14582
ER -