Early Blood Test Patterns Linked to Three-Year Kidney Transplant Outcomes

Kidney transplant recipients require ongoing monitoring to detect allograft injury, rejection, and graft loss. Early elevations in donor-derived cell-free DNA (dd-cfDNA) have often been attributed to perioperative injury, making their clinical significance difficult to interpret. However, a new analysis linking early dd-cfDNA patterns to kidney allograft outcomes over three years suggests that these elevations may provide valuable insights into long-term graft health.

CareDx (Brisbane, CA, USA) announced the publication of the third analysis from the Kidney Allograft Outcomes AlloSure Registry (KOAR) in Transplantation. The multicenter study evaluated 1,137 kidney transplant recipients across 56 centers, examining the relationship between AlloSure Kidney dd-cfDNA measurements obtained during the first four months after transplantation and subsequent graft dysfunction, rejection, and graft loss.

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Researchers classified patients into four groups based on their early dd-cfDNA trajectories: consistently low levels, transient elevations, late elevations, and persistent elevations. Multivariable analyses assessed the association between these patterns and three-year outcomes. The findings showed that the timing and persistence of elevated dd-cfDNA levels were associated with differences in long-term graft outcomes.

Patients with persistently elevated AlloSure Kidney levels during the first four months had a nine-fold higher incidence of allograft loss than those with consistently low levels. Late elevations were independently associated with donor-specific antibody development, rejection, and graft loss, with 8.8% of patients in this group experiencing graft loss during follow-up.

In contrast, patients whose early dd-cfDNA elevations resolved within four months did not experience significantly worse outcomes. Graft loss occurred in 2.9% of patients with transient elevations, compared with 2.2% of those with consistently low levels. Most recipients (83.7%) maintained low AlloSure Kidney levels during the early post-transplant period and experienced favorable three-year outcomes.

Baseline graft function and rates of delayed graft function were similar across the groups, suggesting that perioperative injury alone did not explain early dd-cfDNA elevations. The findings indicate that longitudinal molecular testing may help distinguish temporary changes from persistent or emerging signs of graft injury, potentially identifying patients who require closer surveillance before clinical dysfunction becomes apparent.

AlloSure Kidney is a noninvasive blood test that measures donor-derived cell-free DNA released into the recipient's circulation following kidney transplantation. Elevated levels may indicate injury to the transplanted organ. The test is designed to support ongoing allograft monitoring and risk assessment, providing molecular information alongside conventional clinical and laboratory evaluations.

“Our findings show that the pattern of dd-cfDNA changes during the first four months after transplantation can predict long-term graft outcomes,” said Kalathil Sureshkumar, MD, of Allegheny General Hospital. He added that persistent or later-emerging elevations could help identify patients at greater risk of rejection and graft loss, while resolved elevations were associated with more favorable outcomes.

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