Hirai Toshihito, Banno Taro, Omoto Kazuya, Shimizu Tomokazu, Hidaka Sumi, Kijima Yu, Furusawa Miyuki, Saitoh Ayaka, Unagami Kohei, Inui Masashi, Ishida Hideki, Takagi Toshio
Department of Urology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
Yocho-machi Clinic, Tokyo, Japan.
Clin Transplant. 2025 Jul;39(7):e70221. doi: 10.1111/ctr.70221.
Donor-derived cell-free DNA (dd-cfDNA) offers a non-invasive biomarker for detecting allograft injury. However, its performance in predominantly living-donor transplant settings in Asian populations remains underexplored.
In a multicenter prospective pilot study, 73 living-donor kidney transplant (LKT) recipients from Japan underwent plasma dd-cfDNA testing and protocol biopsies approximately 1 year post-transplant. Diagnostic performance of dd-cfDNA for subclinical antibody-mediated rejection (AMR) was evaluated at 1.0% and 0.5% cut-off thresholds.
Eight patients (11.0%) were diagnosed with subclinical active AMR. Patients with dd-cfDNA ≥1.0% showed significantly higher incidence of AMR compared to those with dd-cfDNA <1.0% (80% vs. 5.9%, p < 0.001). ROC analysis revealed an AUC of 0.85 for dd-cfDNA in diagnosing AMR. Lowering the threshold to 0.5% improved sensitivity while maintaining high specificity. Patients with persistent donor-specific antibodies (DSA) at 1-year follow-up exhibited significantly higher dd-cfDNA levels. Neither HLA nor ABO incompatibility nor donor-recipient relation significantly affected dd-cfDNA levels.
dd-cfDNA demonstrates high negative predictive value and complements DSA testing for early detection of subclinical AMR in living-donor transplants. This pilot study provides foundational evidence for dd-cfDNA-based surveillance strategies in Asian cohorts.
供体来源的游离DNA（dd-cfDNA）为检测同种异体移植损伤提供了一种非侵入性生物标志物。然而，其在亚洲人群主要为活体供体移植环境中的表现仍未得到充分研究。
在一项多中心前瞻性试点研究中，73名来自日本的活体供肾移植（LKT）受者在移植后约1年接受了血浆dd-cfDNA检测和方案活检。在1.0%和0.5%的截断阈值下评估dd-cfDNA对亚临床抗体介导排斥反应（AMR）的诊断性能。
8名患者（11.0%）被诊断为亚临床活动性AMR。dd-cfDNA≥1.0%的患者与dd-cfDNA<1.0%的患者相比，AMR发生率显著更高（80%对5.9%，p<0.001）。ROC分析显示，dd-cfDNA诊断AMR的AUC为0.85。将阈值降低到0.5%可提高敏感性，同时保持高特异性。在1年随访中持续存在供体特异性抗体（DSA）的患者表现出显著更高的dd-cfDNA水平。HLA、ABO不相容性或供受者关系均未显著影响dd-cfDNA水平。
dd-cfDNA显示出高阴性预测价值，并补充了DSA检测，用于早期检测活体供体移植中的亚临床AMR。这项试点研究为亚洲队列中基于dd-cfDNA的监测策略提供了基础证据。
