Prognostic value of the donor‐derived cell‐free DNA assay in acute renal rejection therapy: A prospective cohort study

Shen, Jia; Guo, Luying; Yan, Pengpeng; Zhou, Jingyi; Zhou, Qin; Lei, Wenhua; Liu, Haitao; Liu, Guangjun; Lv, Junhao; Feng, Lin; Huang, Hongfeng; Dong, Wenzhao; Shu, Liping; Wang, Huiping; Wu, Jiang; Chen, Jianghua; Wang, Rending

doi:10.1111/ctr.14053

Cited by 19 publications

(11 citation statements)

References 35 publications

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“…We performed a single-center retrospective study that included donation of citizen death or living donor kidney transplant recipients with matched allograft biopsies in our hospital from March 2017 to September 2019. The inclusion criteria consisted of the following: 1) patients aged 18 years or above; 2) patients showing a decline of graft function more than 20% from nadir ( 22 ). The exclusion criteria consisted of the following: 1) recurrent/ de novo glomerulonephritis; 2) BK polyomavirus nephropathy and other infectious diseases; 3) chronic calcineurin inhibitor nephrotoxicity; 4) multiorgan or repeated kidney transplantation.…”

Section: Methodsmentioning

confidence: 99%

Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts

et al. 2022

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Recent studies have confirmed the role of plasma donor-derived cell-free DNA (ddcfDNA) as a reliable non-invasive biomarker for allograft injury after kidney transplantation. Whereas the variability of plasma ddcfDNA levels among recipients has limited their clinical use. This study aimed to explore the intrinsic factors associated with plasma ddcfDNA elevation by investigating the impact of Banff lesions and inflammatory infiltrates on ddcfDNA levels in kidney transplant recipients. From March 2017 to September 2019, a total of 106 kidney transplant recipients with matched allograft biopsies were included, consisting of 13 recipients with normal/nonspecific changes, 13 recipients with borderline changes, 60 with T cell-mediated rejection, and 20 with antibody-mediated rejection. Histologic classification was performed according to the Banff 2017 criteria by two experienced pathologists. Plasma ddcfDNA fractions ranged from 0.12% to 10.22%, with a median level of 0.91%. Banff histology subelements including glomerulitis, intimal arteritis, and severe interstitial inflammation were correlated with increased plasma ddcfDNA levels. The inflammatory cell infiltrate in the allografts was phenotyped by immunochemistry and automatically counted by digital image recognition. Pearson correlation analysis revealed a significant positive correlation between macrophage infiltrations in allografts and plasma ddcfDNA levels. Additionally, macrophage extracellular trap (MET) activity was significantly associated with the rise in plasma ddcfDNA levels. Our findings demonstrated that plasma ddcfDNA could reflect the inflammatory state in renal allografts and suggested the potential role of METs in the pathogenesis of allograft injury.

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Section: Methodsmentioning

confidence: 99%

Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts

et al. 2022

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“…The levels of dd-cfDNA are affected by anti-rejection therapy and are dose-dependent. Levels of dd-cfDNA decrease rapidly after anti-rejection therapy [57]. This paves the way for us to create personalized immunosuppressive drugs to prevent graft damage and rejection.…”

Section: Monitoring Of Organ Damage and Rejection Through Dd-cfdnamentioning

confidence: 96%

Donor-Derived Cell-Free DNA to Diagnose Graft Rejection Post-Transplant: Past, Present and Future

Kumar

Rana

et al. 2021

Transplantology

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Donor-derived cell-free DNA (dd-cfDNA) is a non-invasive biomarker that is more sensitive and specific towards diagnosing any graft injury or rejection. Due to its applicability over all transplanted organs irrespective of age, sex, race, ethnicity, and the non-requirement of a donor sample, it emerges as a new gold standard for graft health and rejection monitoring. Published research articles describing the role and efficiency of dd-cfDNA were identified and scrutinized to acquire a brief understanding of the history, evolution, emergence, role, efficiency, and applicability of dd-cfDNA in the field of transplantation. The dd-cfDNA can be quantified using quantitative PCR, next-generation sequencing, and droplet digital PCR, and there is a commendatory outcome in terms of diagnosing graft injury and monitoring graft health. The increased levels of dd-cfDNA can diagnose the rejection prior to any other presently used biochemistry or immunological assay methods. Biopsies are performed when these tests show any signs of injury and/or rejection. Therefore, by the time these tests predict and show any unusual or improper activity of the graft, the graft is already damaged by almost 50%. This review elucidates the evolution, physiology, techniques, limitations, and prospects of dd-cfDNA as a biomarker for post-transplant graft damage and rejection.

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“…Shen et al [ 97 ] analysed 77 blood samples of 28 AR patients (5 with ABMR and 23 with TCMR). The amounts of total cfDNA and dd-cfDNA were measured before and after anti-rejection therapy.…”

Section: Cfdna In Kidney Transplantationmentioning

confidence: 99%

Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review

Martuszewski

Paluszkiewicz

Król

et al. 2021

JCM

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Kidney transplantation (KTx) is the best treatment method for end-stage kidney disease. KTx improves the patient’s quality of life and prolongs their survival time; however, not all patients benefit fully from the transplantation procedure. For some patients, a problem is the premature loss of graft function due to immunological or non-immunological factors. Circulating cell-free DNA (cfDNA) is degraded deoxyribonucleic acid fragments that are released into the blood and other body fluids. Donor-derived cell-free DNA (dd-cfDNA) is cfDNA that is exogenous to the patient and comes from a transplanted organ. As opposed to an invasive biopsy, dd-cfDNA can be detected by a non-invasive analysis of a sample. The increase in dd-cfDNA concentration occurs even before the creatinine level starts rising, which may enable early diagnosis of transplant injury and adequate treatment to avoid premature graft loss. In this paper, we summarise the latest promising results related to cfDNA in transplant patients.

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Prognostic value of the donor‐derived cell‐free DNA assay in acute renal rejection therapy: A prospective cohort study

Cited by 19 publications

References 35 publications

Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts

Plasma Donor-Derived Cell-Free DNA Levels Are Associated With the Inflammatory Burden and Macrophage Extracellular Trap Activity in Renal Allografts

Donor-Derived Cell-Free DNA to Diagnose Graft Rejection Post-Transplant: Past, Present and Future

Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review

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