Department of Nephrology and Kidney Transplantation, School of Medicine, General Hospital of Athens Laiko, National and Kapodistrian University of Athens, Athens, Greece.
"Genotypos" Science Laboratory of Molecular Genetic and Cytogenetics, Athens, Greece.
Transpl Int. 2023 Oct 13;36:11507. doi: 10.3389/ti.2023.11507. eCollection 2023.
In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646-0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3-2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21-0.51, = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA's ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR.
在我们的前瞻性、单中心队列研究中,我们收集了 30 名新接受肾移植患者的血液样本,在第 1、2、3 和 5 个月进行 dd-cfDNA 分析,同时进行肌酐/eGFR 和 DSA 监测,并收集了 32 名接受指示性活检的患者的血液样本,他们的 dd-cfDNA 水平在活检时和 1 个月后进行了测量。在活检组中,14 名患者(43.8%)被诊断为 TCMR,5 名患者(15.6%)被诊断为 ABMR。dd-cfDNA 在诊断活检患者的排斥反应方面优于肌酐。当选择 dd-cfDNA 阈值为 0.5%时,灵敏度为 73.7%,特异性为 92.3%(AUC:0.804,0.646-0.961)。在排斥反应患者中,活检前的 dd-cfDNA 水平(0.94%,0.3-2.0)在开始治疗后显著下降,中位数在 1 个月时已恢复到基线水平(0.33%,0.21-0.51, = 0.0036)。在监测组中,移植后第二个月的 dd-cfDNA 水平较高(>0.5%)与移植后 1 年内 eGFR 无增加相关。该研究首次在肾移植监测中使用 AlloSeq 试剂盒,证实了 dd-cfDNA 检测排斥反应、监测治疗以及预测 eGFR 长期预后较差的能力。