Improved Test Using Donor-Derived Cell-Free DNA Promising for Kidney Graft Rejection

By Megan Brooks

November 19, 2021

NEW YORK (Reuters Health) - A new test that combines both the fraction and quantity of donor-derived cell-free DNA (dd-cfDNA), with the previously validated percent dd-cfDNA, is more sensitive in detecting active kidney-allograft rejection, compared to an older version of the test that used dd-cfDNA fraction alone.

The new Prospera with Quantification test, from Natera Inc, is the only available cfDNA test for kidney rejection that provides all three values (quantity, fraction and total cfDNA) on every report, according to a company press release.

"Total cell-free DNA is often elevated during viral infections and other complicated scenarios due to increases in the host-derived fraction," Dr. Suphamai Bunnapradist, a transplant nephrologist at the University of California, Los Angeles (UCLA), said in the release.

"Consequently, the percentage of dd-cfDNA can be artificially depressed in these scenarios, leading to false negative results. The absolute quantification of dd-cfDNA in the sample is a game-changer as it makes the test more robust in challenging clinical scenarios, while boosting its sensitivity," Dr. Bunnapradist said.

Dr. Bunnapradist is first author on a new study in the Journal of the American Society of Nephrology that assessed the test's performance in 41 kidney-transplant patients being managed at UCLA Medical Center.

Matched biopsy and dd-cfDNA test results were available for 16 patients; active rejection was found in nine of 16 (56%) biopsies, with five classified as T cell-mediated rejection, one as antibody-mediated rejection, and three as mixed type (antibody-mediated rejection/T cell-mediated rejection).

Compared with the original test, the new Prospera with Quantification test, incorporating the quantity of dd-cfDNA with the fraction of dd-cfDNA, improved the sensitivity of the test from seven of nine (77.8% sensitivity) to nine out of nine (100%) cases of active rejection, while maintaining high specificity, the authors report.

"Early detection of allograft rejection is critical to the successful management of transplant recipients. This test looks for damage really early on and is more accurate" than the original test, Dr. Bunnapradist noted in a phone interview with Reuters Health.

Bernie Tobin, general manager of organ health at Natera, told Reuters Health by email, "We encourage physicians to consider Natera's Prospera transplant assessment test for every kidney transplant patient to monitor the health of the allograft."

"We know that this test can improve outcomes for patients," Tobin said, "and within clinical practice, physicians are ordering the tests based on two scenarios: 1) Surveillance: The Prospera test may be used to monitor the health of the transplanted kidney at regular intervals, in the absence of any symptoms of active rejection. In a surveillance situation, we recommend testing at 1, 2, 3, 4, 6, 9, and 12 months; 2) When clinically indicated: Here, the test is used by nephrologists considering the diagnosis of active rejection, helping to rule in or out this condition when evaluating the need for a biopsy."

"Natera's Prospera transplant assessment test is covered by Medicare for all kidney transplants, including repeat transplants. We look forward to partnerships with commercial payers to ensure this test is accessible, available and covered for all transplant patients," Tobin told Reuters Health.

Natera sponsored the study. Dr. Bunnapradist and several coauthors report financial ties to the company.

SOURCE: Journal of the American Society of Nephrology (JASN), October 2021.