Detecting a Silent Threat – Transplant Rejection

Optimising outcomes for kidney transplant patients

Kidney transplantation is universally recognised as the best treatment option for patients with endstage renal disease. Although clinical outcomes of kidney transplantation have improved steadily for decades, transplant rejection remains one of the key challenges to long-term patient survival. Eurofins’ TruGraf® test is the first test capable of reliably ruling out “silent” subclinical acute rejection in patients with stable renal function, where a patient’s immune system can reject a kidney transplant without the patient showing any other clinical symptoms.

Based on data from the World Health Organization (WHO)’s global database on organ donation and transplantation, between 2015 and 2020, over 80,000 kidney transplants were performed across the world annually. Kidney transplantation can be a lifesaving procedure and can extend a patient’s life expectancy by up to 20 years. Transplant rejection is a concern for all patients though: silent or subclinical acute transplant rejection is prevalent in 25% of those who receive new kidneys within the first year. Patients may develop significant anxiety about the possibility of their organ rejecting silently, so tools for rejection management are extremely important in helping physicians secure the best outcomes for their patients.

Post kidney transplantation, the right levels of immunosuppression are key. Immunosuppressant drugs weaken a patient’s immune system in order to reduce their body’s reaction to the foreign organ. While the dosage may be lowered over time, patients are prescribed lifelong immunosuppressive antirejection medications, and often go through life concerned about the stability of their transplant. Post-transplantation patient monitoring has typically involved both testing for immunosuppressive drug levels, which indicate whether patients are taking their medications as prescribed, as well as measuring serum creatinine levels, which indicate how well the kidney is filtering the blood. Creatinine is the current Standard of Care indicator of renal function. However, high levels of creatinine are a late indicator of damage already done to a transplanted kidney and pose unnecessary rejection risk to the patient, given that up to 50% of kidney function may already be lost before serum creatinine levels rise.

The current Standard of Care to rule out the presence of “silent” subclinical acute rejection in patients with stable renal function involves performing a “surveillance” organ biopsy. Biopsies are invasive procedures with several difficulties, from sampling error to subjective analysis, logistical challenges for patients and transplant centres, and potential complications and significant pain for the patient. Given their high cost, they are not performed regularly. 80% return negative (i.e. normal) results, leaving patients unnecessarily subjected to the associated risks and pain of a biopsy.

Eurofins Transplant Genomics launched TruGraf® in late 2019 – the first and only blood test that can rule out “silent” subclinical acute rejection in kidney transplant recipients with stable renal function. This non-invasive test allows doctors to reassure patients with stable renal function that their kidney transplant is not harbouring silent rejection by assessing whether they are adequately immunosuppressed. As a result, the test avoids the need for invasive, risky and costly surveillance biopsies, and allows for early detection of rejection risk, not just when rejection is suspected.

Eurofins Transplant Genomics worked with leading researchers at Northwestern University’s Comprehensive Transplant Center and The Scripps Research Institute to develop TruGraf®. Test results support clinicians with information to optimise immune-suppressive therapy, enhance patient care and improve transplant survival.

Most recently, Eurofins Transplant Genomics launched OmniGraf™, the first and only non-invasive test panel for the earliest and most accurate view of kidney transplant rejection. OmniGraf™ combines novel genetic biomarkers by bringing together Eurofins Transplant Genomics’ TruGraf® blood gene expression test and Eurofins Viracor’s TRAC® donor-derived cell-free DNA assays.

Eurofins Viracor’s TRAC® (Transplant Rejection Allograft Check) donor-derived cell-free DNA (dd-cfDNA) assay relies on non-invasive liquid biopsy to monitor the percentage of dd-cfDNA in a patient’s plasma post-transplant, using Next Generation Sequencing (NGS). As donor-derived cell-free DNA is released when the transplant organ is attacked by the host’s immune system, monitoring dd-cfDNA levels can indicate whether the patient is likely to be experiencing transplant rejection.

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