TRANSPLANT MONITORING
Donor-derived cfDNA as a non-invasive biomarker in transplant monitoring
Stephanie Anderson considers the clinical limitations of creatinine and biopsy in post-kidney transplant monitoring, and the case for donor-derived cell-free DNA as an early, non-invasive biomarker.
Allograft rejection remains a significant global challenge, contributing to the loss of thousands of transplanted organs annually and resulting in substantial patient morbidity, mortality, and diminished quality of life.1
In the UK
alone, approximately 3,000 kidney transplants are performed annually, with a follow up population of over 45,000 patients.2
In kidney transplantation, rejection
affects approximately 20% of recipients within the first year, imposing a considerable economic burden on healthcare systems due to the costs associated with graft failure and the subsequent need for dialysis.1
damage may already be present by the time a rise in serum creatinine is evident. Biopsies, although gold standard for diagnosing rejection and graft damage, are not desirable for routine monitoring because they are invasive, expensive
and risk complications.3,4 Detection of
circulating donor-specific anti-human leucocyte antigen antibodies (anti- HLA DSA) are indicative of suspected antibody mediated issues but may not be detected before any graft damage has occurred. It is apparent that there is a need for more sensitive and earlier biomarkers to improve personalised immunosuppression in organ transplantation to reduce premature graft loss.1,3,4
Donor-derived cell-free DNA (dd- cfDNA) is an emerging non-invasive biomarker that has the potential to detect allograft injury at a much earlier stage
Accurate
and timely detection of allograft rejection, along with effective immunosuppression, is critical for ensuring long-term graft survival.
The current approach to monitoring
rejection in kidney transplantation is based on decades-old functional markers such as serum creatinine and estimated glomerular filtration rate (eGFR) and proteinuria. However, there are limitations to these tests. For example, serum creatinine is a measure of kidney function rather than graft injury, and an increase in creatinine levels is not specific to allograft injury.3
Elevated serum
creatinine levels may therefore trigger unnecessary biopsies and in addition to this a significant degree of graft
In kidney transplantation, rejection affects approximately 20% of recipients within the first year, imposing a considerable economic burden due to the costs associated with graft failure and the subsequent need for dialysis.
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