Donor-derived cfDNA as a non-invasive biomarker in transplant monitoring

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 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 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.