A study of more than 1,100 transplant recipients found that persistent or later-emerging elevations in donor-derived cell-free DNA were associated with greater risks of rejection and graft loss.

CareDx announced the publication of a third analysis from the Kidney Allograft Outcomes AlloSure Registry (KOAR) in Transplantation. The analysis examined whether early post-transplant levels of AlloSure Kidney donor-derived cell-free DNA (dd-cfDNA) correlate with kidney allograft outcomes at three years.

The multicenter cohort included 1,137 kidney transplant recipients across 56 centers. Researchers sorted recipients into four trajectory groups based on AlloSure Kidney measurements taken within the first four months after transplant: consistently low, transient elevation, late elevation, and persistent elevation. They then applied multivariable models to assess how each group’s trajectory related to three-year outcomes, including allograft dysfunction and graft loss.

Rates of delayed graft function were similar across all groups, suggesting that perioperative injury alone did not explain early AlloSure Kidney elevations. According to CareDx, the findings support the clinical interpretability of the test during the early post-transplant period.

“Early elevations in dd-cfDNA have often been attributed to perioperative injury, leaving uncertainty about their long-term clinical significance,” says Kalathil Sureshkumar, MD, FRCP, FASN, of the Division of Nephrology and Hypertension, Medicine Institute, at Allegheny General Hospital, in a release. He adds that persistent or later-emerging elevations can identify patients at substantially higher risk of rejection and graft loss, while transient elevations that resolve are associated with more favorable outcomes.

Key Findings by Trajectory Group

The analysis reported the following:

  • Patients with persistent AlloSure Kidney elevation during the first four months had a nine-fold higher incidence of allograft loss compared with patients with consistently low levels.
  • Late elevation was independently associated with donor-specific antibody development, rejection, and allograft loss, with graft loss occurring in 8.8% of patients in this group.
  • Transient elevations that resolved within four months were not associated with worse outcomes, with incidence similar to that of recipients with consistently low levels (2.9% vs 2.2%).
  • Most recipients (83.7%) had consistently low AlloSure Kidney levels during the first four months and experienced favorable three-year outcomes, including low rates of graft dysfunction and graft loss.

Baseline graft function was similar across all groups, suggesting that AlloSure Kidney elevations may identify molecular injury before clinical graft dysfunction becomes evident. Sureshkumar says the results reinforce the value of routine early monitoring to help clinicians identify patients who may benefit from closer surveillance.

“The robust evidence provided by the KOAR registry continues to demonstrate the utility of AlloSure Kidney across clinical contexts and throughout the post-transplant course,” says Jeffrey Teuteberg, MD, chief medical officer of CareDx, in a release. He adds that routine use of the test can help clinicians identify which patients may be at higher risk for poor outcomes early after transplant and support personalized care strategies for them.

The full publication is available online in Transplantation.

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