Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.
Akifova, A., et al.Nephrology Dialysis Transplantation 2024 [record in progress].
Aims
This study aimed to determine if monitoring donor-derived cell-free DNA (dd-cfDNA) could lead to early diagnosis of antibody-mediated rejection (AMR) in kidney transplant recipients.
Interventions
Participants were randomly assigned to either dd-cfDNA-guided kidney allograft biopsy or clinician-guided biopsy.
Participants
40 adult kidney transplant recipients > 180 days following kidney transplantation, with prevalent dnDSA and an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2.
Outcomes
The primary outcome was the time from study inclusion to diagnosis of active AMR or chronic active AMR. Secondary outcomes were time from first dnDSA occurrence to the diagnosis of AMR and diagnostic test metrics.
Follow-up
24 months after baseline
CET Conclusions
This small, single-centre RCT investigated the potential role of donor derived cell-free DNA (cfDNA) monitoring in kidney transplant recipients with de-novo DSA. Patients were randomised to routine cfDNA monitoring with biopsy at a threshold of >50 copies/ml, versus biopsy for clinical indication. The primary endpoint of time to diagnosis of antibody mediated rejection (AMR) was significantly shorter in the cfDNA group (2.8 months vs. 14.5 months). There are very few prospective RCTs of biomarkers for post-transplant monitoring, and so the authors should be congratulated. It should be noted that the study is open-label and there is a risk of measurement bias, as biopsies in the control group were at the discretion of the clinical team. Whilst the time to diagnosis was shorter in the cfDNA group, the study is too small to demonstrate whether this improves clinical outcomes through earlier treatment, and so is unable to truly assess the benefits of routine monitoring.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT04897438