How dd-cfDNA Could Transform Monitoring in Kidney Transplant Care
Dr. Stephanie Anderson explores the advantages of dd-cfDNA as a transplant monitoring tool.
Early and accurate detection of rejection remains a major challenge in kidney transplantation, with clinicians still relying on decades-old indicators. There is a growing demand for more sensitive, real-time and patient-friendly tools to improve long-term transplant outcomes and reduce healthcare burden.
Donor-derived cell-free DNA (dd-cfDNA) is emerging as a promising biomarker capable of detecting graft injury earlier and more accurately than traditional methods. This minimally invasive approach is currently being evaluated in a pilot study led by renal specialists at North Bristol NHS Trust (NBT), with the aim of generating real-world evidence to support its broader clinical adoption.
Technology Networks recently spoke with Dr. Stephanie Anderson, product manager, HT Genomics at Promega UK, to learn more about the advantages of dd-cfDNA as a transplant monitoring tool. In this interview, Dr. Anderson also discusses the technology supporting the NBT pilot study and what regulatory and clinical hurdles remain before dd-cfDNA testing can be fully adopted in healthcare.
What are the key limitations of existing kidney transplant monitoring methods?
Stephanie Anderson, PhD (SA):
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.
Serum creatinine, for example, the most commonly used monitoring tool, is a measure of kidney function rather than graft injury, and increased creatinine levels are not specific to allograft injury. By the time you see an increase in serum creatinine, graft injury has already progressed.
Biopsies, although the gold standard for diagnosing rejection and graft damage, are not desirable for routine monitoring because they are invasive, expensive and risk complications.
Detection of circulating donor-specific anti-human leukocyte antigen antibodies (anti-HLA DSA) is indicative of suspected antibody-mediated rejection but may not be detected before any graft damage has occurred.
AM:
SA:
dd-cfDNA is an emerging non-invasive biomarker that has the potential to detect allograft injury at a much earlier stage than existing markers. An increasing number of studies have investigated the clinical validity of tracking dd-cfDNA levels in plasma to identify allograft injury and active rejection.
In essence, injury to the donor kidney releases fragments of donor DNA into the recipient’s bloodstream. Next-generation sequencing assays quantify the donor-derived fraction (percent of total cfDNA) and/or absolute copies/mL, using SNP panels that distinguish donor from recipient without prior genotyping.
Because circulating cfDNA has a short half-life, dd-cfDNA provides a snapshot in real time, not just downstream loss of function.
Potential benefits and drivers behind the NBT pilot study for kidney transplant patients include the logistics of travel and disruption to patients’ lives and routine. Invasive biopsies could be replaced by a simple blood test, detecting graft failure earlier and facilitating personalized immunosuppression.
AM:
SA:
To investigate the utility of cfDNA as a non-invasive alternative to biopsy, particularly in detecting early signs of graft dysfunction in kidney transplant recipients, Dr. Rommel Ravanan and Dr. Ailish Nimmo, renal consultants, along with Dr. Krishnappan Ramanathan, renal registrar, and Claire Adams, transplant nurse specialist at NBT, and the Histocompatibility and Immunogenetics (H&I) laboratory collaborators at NBT are participating in a cfDNA pilot study involving 240 cfDNA tests.
This evaluation has been possible due to the contribution of testing kits by the technology providers and kind contributions from Southmead Hospital Charity. This proof-of-concept study would generate real-world data for future clinical validation and contribute to future NICE evaluation processes.
AM:
SA:
The workflow in this pilot study includes the use of Promega’s new Maxwell RSC Rapid ccfDNA extraction kits. The Maxwell Rapid ccfDNA kit allows extraction of cfDNA from plasma without any pre-processing steps allowing this research to be conducted alongside standard day-to-day H&I testing.
Key to the success of the study would be the quality, yield and consistency of DNA, which the team have been achieving with the Maxwell DNA extraction kits they routinely use for HLA typing. The Maxwell instrument, as stated by Dr. Sarinder Day (clinical lead immunogenetics at the NHSBT H&I lab in Bristol), was adopted for its reliability and consistent high-quality DNA yield.
AM:
SA:
The key step towards full adoption of dd-cfDNA as a biomarker for allograft rejection would be NICE approval. For NHS-wide adoption, NICE will review clinical utility and cost-effectiveness (not just accuracy), develop a scope with defined “contexts of use,” and issue national guidance if evidence is sufficient. Economic models must show system benefit (e.g., avoided biopsies, better graft survival) and address subgroup equity.
The NBT proof of concept study would generate real-world data for future clinical validation and contribute to future NICE evaluation processes. Obviously, the cost-effectiveness of this approach would also need to be considered.
AM:
SA:
Over the next decade, real-time, non-invasive biomarkers such as dd-cfDNA could fundamentally change the management of kidney transplantation. If current pilot studies, such as the one at NBT, prove successful, they could lay the groundwork for the personalized immunosuppression that transplant medicine urgently needs to reduce premature graft loss.
The introduction to this interview includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.
