Increase in nuclear cell‐free DNA is associated with major adverse events in adult and pediatric heart transplant recipients

Zangwill, Steven; Deshpande, Shriprasad; Simpson, Pippa; Liang, Huan; Zhang, Liyun; Dasgupta, Mahua; Richmond, Marc E.; Kindel, Steven J.; Bichell, David P.; Mahle, William T.; Wigger, M.; Schroder, Jacob N.; Knecht, Kenneth R.; Pahl, Elfriede; Gaglianello, Nunzio; North, Paula E.; Tomita‐Mitchell, Aoy; Mitchell, Michael E.

doi:10.1111/ctr.14509

Cited by 2 publications

(3 citation statements)

References 20 publications

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“…As for dd-cfDNA, a preliminary study (Zangwill, 2020) [ 18 ] focused on the first 10 days after heart transplantation in a small pediatric population showed that a blunted decline of initially elevated dd-cfDNA may be associated with early death. Two other studies found that total cfDNA levels greater than 50 ng/mL were associated with increased risk of major events (composite outcome of cardiac arrest, mechanical circulatory support, death) (Zangwill 2022 [ 19 ]), death (Scott, Zangwill 2022 [ 19 , 20 ]) and treatment for infection [ 19 , 20 ].…”

Section: Pico Questions and Recommendationsmentioning

confidence: 99%

“…Of note, several groups have found clear relationships between “total or nuclear cfDNA” (derived both from recipient and donor tissues) and several near-term events, such as death, cardiac arrest, and need for mechanical circulatory support [ 19 ]. Total cfDNA seems to be a marker of more extensive tissue damage, and has demonstrated prognostic value in different ICU patient populations.…”

Section: Pico Questions and Recommendationsmentioning

confidence: 99%

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European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance

Nikolova,

Agbor-Enoh,

Bos

et al. 2024

Transpl Int

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While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field’s incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

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Section: Pico Questions and Recommendationsmentioning

confidence: 99%

Section: Pico Questions and Recommendationsmentioning

confidence: 99%

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance

Nikolova,

Agbor-Enoh,

Bos

et al. 2024

Transpl Int

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“…Lastly, it has to be noted that the use of cell-free DNA in children poses additional problems, linked to the possibility of obtaining enough material from liquid biopsies and to optimizing cut-offs for this population. Recent data, however, have confirmed that in heart transplant recipients, children behave similarly to adults, with cfDNA being a very accurate predictor of rejection episodes [ 70 , 71 ]. The experience with kidney transplants is far more limited, and more studies with larger patient cohorts and longer follow-up are needed determine the impact of dd-cfDNA monitoring during routine follow-up of kidney-transplanted patients (Fig.…”

Section: Biomarkers Of the Future (Table 1 And Fig...mentioning

confidence: 99%

Rejection markers in kidney transplantation: do new technologies help children?

Peruzzi

Deaglio

2023

Pediatr Nephrol

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Recent insights in allorecognition and graft rejection mechanisms revealed a more complex picture than originally considered, involving multiple pathways of both adaptive and innate immune response, supplied by efficient inflammatory synergies. Current pillars of transplant monitoring are serum creatinine, proteinuria, and drug blood levels, which are considered as traditional markers, due to consolidated experience, low cost, and widespread availability. The most diffuse immunological biomarkers are donor-specific antibodies, which are included in routine post-transplant monitoring in many centers, although with some reproducibility issues and interpretation difficulties. Confirmed abnormalities in these traditional biomarkers raise the suspicion for rejection and guide the indication for graft biopsy, which is still considered the gold standard for rejection monitoring. Rapidly evolving new “omic” technologies have led to the identification of several novel biomarkers, which may change the landscape of transplant monitoring should their potential be confirmed. Among them, urinary chemokines and measurement of cell-free DNA of donor origin are perhaps the most promising. However, at the moment, these approaches remain highly expensive and cost-prohibitive in most settings, with limited clinical applicability; approachable costs upon technology investments would speed their integration. In addition, transcriptomics, metabolomics, proteomics, and the study of blood and urinary extracellular vesicles have the potential for early identification of subclinical rejection with high sensitivity and specificity, good reproducibility, and for gaining predictive value in an affordable cost setting. In the near future, information derived from these new biomarkers is expected to integrate traditional tools in routine use, allowing identification of rejection prior to clinical manifestations and timely therapeutic intervention. This review will discuss traditional, novel, and invasive and non-invasive biomarkers, underlining their strengths, limitations, and present or future applications in children.

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Increase in nuclear cell‐free DNA is associated with major adverse events in adult and pediatric heart transplant recipients

Cited by 2 publications

References 20 publications

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance

Rejection markers in kidney transplantation: do new technologies help children?

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