Cell-free DNA for the detection of kidney allograft rejection.
A large international study found that a simple blood test measuring DNA shed by the transplanted kidney can flag rejection earlier and more accurately than routine monitoring alone. It also picked up rejection in patients whose kidney function still looked stable.
Background
Kidney allograft rejection is usually confirmed by biopsy, an invasive procedure that cannot be repeated often enough for true surveillance. Donor-derived cell-free DNA (dd-cfDNA) is a non-invasive blood biomarker of allograft injury, but its added value beyond routine monitoring parameters had not been established in a large, population-based setting.
Study design
Investigators enrolled 2,882 kidney allograft recipients across 14 transplant centres in Europe and the United States, with a primary analysis in 1,134 patients and external validation cohorts totalling 1,748 patients, including a cohort of 439 African American patients.
Key findings
dd-cfDNA levels correlated strongly with antibody-mediated rejection, T cell-mediated rejection and mixed rejection (all P < 0.0001). In multivariable analysis dd-cfDNA remained associated with rejection independently of standard-of-care monitoring (odds ratio 2.275; 95% CI 1.902-2.739; P < 0.0001). Adding dd-cfDNA to a standard-of-care prediction model improved discrimination from an area under the curve of 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852; P = 0.0011), with better calibration. dd-cfDNA also showed high predictive value for subclinical rejection in clinically stable patients.
Clinical implications
For transplant units, these data support using dd-cfDNA alongside creatinine and donor-specific antibody monitoring to refine which patients need a biopsy, and to detect subclinical rejection that conventional surveillance would miss. It complements rather than replaces histology.
Category
Transplant
Source
Nature Medicine
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