Session Time: 4:30pm-5:30pm
Presentation Time: 4:45pm-4:50pm
*Purpose: Donor-derived cell-free DNA (dd-cfDNA) as a marker of injury can serve to quantify subclinical inflammation and molecular injury. As the release of graft genomic material is ongoing into recipient’s circulation, such processes may contribute to recipient immune sensitization. Donor-derived nucleic acids, as reflected in elevated dd-cfDNA levels, may result in leucocyte activation, cytokine release, and de novo donor specific antibody (dnDSA) formation. We hypothesized elevated dd-cfDNA levels may predict subsequent HLA dnDSA development after kidney transplant (KT).
*Methods: 961 patients from the prospective multicenter Assessing dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL study; clinicaltrials.gov: NCT04566055219) were examined. All patients had dd-cfDNA (AlloSure®; CareDx) levels monitored during standard post-KT surveillance and paired HLA DSA testing, with all clinical events captured. An elevated dd-cfDNA was defined as >0.5% based on the injury analysis performed within ADMIRAL cohort.
*Results: Multivariable Cox proportional hazards regression analysis [FIGURE 1] supported an effect size of 1.2 (p =0.004), for dd-cfDNA, indicating 20% increased risk of dnDSA for every 1% increase in the dd-cfDNA level. The majority of dnDSA were diagnosed within the 1st year post-KT. The median elevation of dd-cfDNA was 291 days preceding detection of dnDSA, suggesting elevations of dd-cfDNA may happen ahead of DSA formation. By dichotomizing the continuous dd-cfDNA predictor at a threshold 0.5% (low: <0.5%) - case-control numbers shown in TABLE 1 – a significantly increased hazard ratio (HR) of 2.57 (p=0.003) for development of dnDSA was observed. [FIGURE 2].
*Conclusions: Higher dd-cfDNA levels appear to precede the development of dnDSA after KT. A potential causal relationship of dd-cfDNA and dnDSA will require further study. A prospective interventional study, implementing dd-cfDNA monitoring and real-time targeted immunomodulation in response to dd-cfDNA levels, may provide significant value to patient care.
To cite this abstract in AMA style:Gupta G, Alhamad T, Bowers V, Moinuddin I, Ghosh S, Zeng J, Stites E, Pai A, Bromberg JS, Anand S. High Donor-Derived Cell-Free DNA Levels Predict Development of De Novo HLA Donor-Specific Antibodies After Kidney Transplantation – Data from the ADMIRAL Study [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/high-donor-derived-cell-free-dna-levels-predict-development-of-de-novo-hla-donor-specific-antibodies-after-kidney-transplantation-data-from-the-admiral-study/. Accessed June 16, 2021.
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