Early Detection of Kidney Rejection Using Donor DNA Monitoring

The feasibility and acceptability of donor-derived cell-free DNA (dd-cfDNA) for the detection of antibody mediated rejection (AMR) in kidney transplant recipients was the focus of a recently conducted small scale preliminary trial. The results were reported in Nephrology Dialysis Transplantation (1^✔ ✔Trusted Source
Donor DNA Monitoring Permits Earlier Diagnosis of Antibody-Mediated Kidney Rejection

Go to source). The trial involved 40 KTR who developed de novo donor-specific anti-HLA antibodies (dnDSA) but no prior history of renal biopsy-proven AMR. Participants were divided into two groups: an intervention group, in which the biopsy was based on the dd-cfDNA concentration higher than 50cp/mL, and the control group in which the biopsy was performed under clinical indications. The study required an eGFR of at least 20 mL/min/1.73m² at the baseline, although this rate was declining in certain patient groups over time.

Early Diagnosis of Antibody-Mediated Rejection with Donor DNA Monitoring

Thirteen patients in each group underwent biopsies over a 12-month period. Antibody-mediated rejection occurred in 7 patients in the intervention group and 5 in the control group. Indeed, the diagnosis was done at a relatively earlier time in the interventional arm compared to the control arm with a median of 2.8 months as compared to 14.5 months.

Dr Akifova and her team stressed that biopsy at the time of clinical suspicion more commonly yields chronic rejection and stem fibrotic alterations. On the other hand, protocol biopsies for dnDSA usually do not provide clear findings. Thus, monitoring of dd-cfDNA has a high accuracy of 77% for positive prediction and 85% for negative prediction of ABMR, making it a reliable early detection tool for rejection.

Implications for Patient Care

Early rejection, within a therapeutic window allows for timely intervention, preventing graft failure and patient loss. New strategies under development include the CD38 monoclonal antibody, felzartamab, which may improve the therapy.

Altogether, this trial provides encouraging experience that dd-cfDNA may help transform the post-transplant management by detecting AMR earlier and more effectively.

Reference:

1. Donor DNA Monitoring Permits Earlier Diagnosis of Antibody-Mediated Kidney Rejection - (https://www.renalandurologynews.com/news/donor-dna-monitoring-permits-earlier-diagnosis-of-antibody-mediated-kidney-rejection/ )

Source-Medindia