Donor-derived cell-free DNA indicative of allograft injury, eGFR decline
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Donor-derived cell-free DNA was determined to be a leading indicator of allograft injury, eGFR decline, formation of de novo donor-specific antibodies and subclinical rejection, according to published data.
Further, persistently low donor-derived cell-free DNA (dd-cfDNA) may be a predictor of allograft quiescence, or absence of injury, in patients.
“While the effectiveness of dd-cfDNA has been established in clinical trials, its utility in routine clinical practice has not been well described,” Lihong Bu, MD, PhD, University of Minnesota, and colleagues wrote.
The Assessing AlloSure Dd-cfDNA, Monitoring Insights of Renal Allografts with Longitudinal Surveillance (ADMIRAL) study is a multicenter, observational cohort study of kidney transplant recipients. The patients were monitored for up to 3 years with dd-cfDNA. Researchers documented the “effectiveness of dd-cfDNA in identifying allograft rejection and subclinical changes in a real-world setting and evaluate the relationship between dd-cfDNA measurements and non-immune allograft injury,” according to the study.
Researchers evaluated 1,094 kidney transplant recipients from seven transplant centers periodically between June 2016 and January 2020. Each center measured dd-cfDNA at regular intervals, which was included in surveillance testing and diagnostic aid in patients with clinically evident graft dysfunction. Patients who experienced a change in creatinine, worsening proteinuria or the development of dnDSA underwent renal transplant biopsies, which were further evaluated by researchers.
Patients were categorized as high dd-cfDNA ( 0.5%) and low dd-cfDNA (<0.5%) for further evaluation. Using multivariate logistic regression, researchers determined which independent covariates were indicative of high dd-cfDNA measurements.
“ADMIRAL aimed to characterize the relationship between elevation in dd-cfDNA and important predictors of long-term graft survival, including eGFR and formation of dnDSA,” Bu and colleagues wrote.
Researchers found increased dd-cfDNA correlated with both clinical and subclinical allograft rejection. Similarly, dd-cfDNA values of 0.5% or greater correlated with almost a three-fold increase in risk development of dnDSA; specifically, elevated dd-cfDNA values occurred a median of 91 days head of donor specific antibody detection. Researchers also determined that consistently high values of dd-cfDNA indicated more than a 25% decrease in a patient’s eGFR over 3 years.
“Our findings further expand the base of knowledge on interpretation of dd-cfDNA levels in various clinical contexts, showing broader utility as a leading indicator ahead of clinical presentations of allograft injury, formation of dnDSA, eGFR decline and subclinical rejection,” Bu and colleagues wrote. “Additional interventional studies are underway to help better define how the information provided by dd-cfDNA can be used to guide clinical practice and decisions regarding immunomodulation, management of infection, treatment of all types of rejection, and control or even prevent the formation of dnDSA.”
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