New assay may more precisely detect allograft rejection after kidney transplant
A donor-derived cell-free DNA assay from Natera Inc. detected allograft rejection earlier and more precisely than other currently available tests for patients who have undergone kidney transplant, regardless of donor-recipient relationships, according to published study results.
“The analytical validation study clearly shows that Natera’s donor-derived cell-free DNA assay for detecting the risk of kidney transplant rejection is highly accurate and precise and demonstrates superior performance (coefficient of variation up to five times better) than previously published studies,” Allison Ryan, PhD, vice president of data science at Natera, told Healio/Nephrology. “Natera attributes this highly precise performance to its core cell-free DNA technology, single-nucleotide polymorphism-based method and deep experience in clinical testing of over 1.5 million cell-free DNA mixtures including prenatal genetic testing and more recently oncology applications.”
To evaluate the analytical performance of the assay, researchers collected whole blood samples from 31 healthy volunteers and from six patients who had kidney transplant. Researchers considered 66 unique samples with 1,064 replicants, which included cell line-derived reference samples and plasma-derived mixtures. The donor-derived cell-free DNA fraction was then quantified in both related and unrelated donor-recipient pairs and the limit of blank, limit of detection/quantitation, linearity, accuracy and precision were calculated.
Researchers found the donor-derived cell-free DNA assay had a limit of blank of 0.11% and a limit of detection/quantitation of 0.15% for unrelated donors. For related donors, the assay had a limit of blank of 0.23% and a limit of detection/quantitation of 0.29%. Linearity, accuracy and precision were equivalent between unrelated and related donors.
In addition, researchers determined the measurement precision of coefficient of variation was 1.8% and was less than 5% for all other reproducibility measures.
According to Ryan, the precise measurement of donor fraction in cell-free DNA is a more accurate biomarker for detecting organ rejection than eGFR, which is the current standard of care for non-invasive organ testing.
“There is a great need for earlier, more precise non-invasive tools to monitor allograft injury and rejection,” Ryan said. “In the United States, there are more than 190,000 people living with a kidney transplant and it is estimated that 20% to 30% of organ transplants fail within 5 years and approximately 50% fail within 10 years. The current tools for diagnosing organ transplant rejection are either invasive (biopsies) or inaccurate (serum creatinine), creating a strong unmet need for better diagnostic tools to improve patient management and outcomes. Natera is committed to leveraging its cell-free DNA expertise to delivering a test that will accurately detect organ transplant rejection earlier so that patients’ immunosuppression levels can be optimized before irreversible organ damage occurs.” – by Melissa J. Webb
Disclosures: All authors report being employed by Natera.