D118 - Impact of HLA Mismatch on Baseline Donor-Derived Cell-Free DNA in Kidney Transplant Recipients

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Author Block: A. Conant¹, K. Mohib², K. Nashar¹, R. Daloul¹, K. Sureshkumar¹, ¹Allegheny Health Network, Pittsburgh, PA, ²CareDx, San Francisco, CA
*Purpose: Donor derived-cell free DNA (dd-cfDNA) predicts acute rejection earlier in renal allografts. Baseline dd-cfDNA levels are <1% in 96% of kidney transplant recipients (KTRs). Higher levels of human leukocyte antigen (HLA) mismatches could increase recipient immune response to donor antigens. We evaluated the impact of HLA mismatches on baseline dd-cfDNA values in KTRs.
*Methods: We identified KTRs between April 2018 and August 2025 at our center who had dd-cfDNA (AlloSure, CareDx, Brisbane, CA) levels at 4- 8 weeks post-transplantation. Those with baseline dd-cfDNA levels <1.0% were included in the analysis. Baseline dd-cfDNA levels were compared between KTRs with HLA mismatches 0-3 vs. HLA mismatches 4-6. Comparison was also done between patients with HLA-DR 0-1 vs. 2 mismatches.
*Results: There were 58 patients included in the analysis. All patients received induction with Thymoglobulin. Out of all the patients, 17 were in HLA 0-3 mismatch group and 41 in HLA 3-6 mismatch group. HLA-DR mismatches were 0-1 in 38 patients and 2 in 20 patients. There were no significant differences in baseline dd-cfDNA values between HLA mismatches 0-3 vs. 4-6 groups (0.25[0.16-0.38] vs. 0.21 [0.16-0.33], p=0.45). Similarly, there were no significant differences in dd-cfDNA levels between patients with 0-1 vs. 2 HLA-DR mismatches (0.21[0.14-0.31 vs. 0.26 [0.18-0.41], p=0.23) (figure 1).
*Conclusions: Our study showed no differences in baseline dd-cfDNA values at different levels of HLA and HLA-DR mismatches. Profound immunosuppression in the early post-transplant period related to the use of perioperative induction therapy could be one possible explanation for this finding.