Division of Nephrology, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California.
Biostatistics Core, Research Institute and General Clinical Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
Am J Transplant. 2019 Jun;19(6):1663-1670. doi: 10.1111/ajt.15289. Epub 2019 Mar 29.
Donor-derived cell-free DNA (dd-cfDNA) became Medicare reimbursable in the United States in October 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial, but it has not yet been externally validated. We assessed 63 adult kidney transplant recipients with suspicion of rejection with dd-cfDNA and allograft biopsy. Of these, 27 (43%) patients had donor-specific antibodies and 34 (54%) were found to have rejection by biopsy. The percentage of dd-cfDNA was higher among patients with antibody-mediated rejection (ABMR; median 1.35%; interquartile range [IQR]: 1.10%-1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%-1.10%; P < .001) and cell-mediated rejection (CMR; median: 0.27%, IQR: 0.19%-1.30%; P = .01). The dd-cfDNA test did not discriminate patients with CMR from those without rejection. The area under the ROC curve (AUC) for CMR was 0.42 (95% CI: 0.17-0.66). For ABMR, the AUC was 0.82 (95% CI: 0.71-0.93) and a dd-cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%. The dd-cfDNA test did not discriminate CMR from no rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR.
供体来源的无细胞 DNA（dd-cfDNA）于 2017 年 10 月在美国成为医疗保险可报销的项目，用于检测肾移植受者排斥反应，其依据是一项关键性验证试验的结果，但尚未经过外部验证。我们对 63 例疑似排斥反应的成年肾移植受者进行了 dd-cfDNA 和移植肾活检检查。其中 27 例（43%）患者存在供体特异性抗体，34 例（54%）通过活检发现排斥反应。与无排斥反应（中位数 0.38%，IQR：0.26%-1.10%；P<0.001）和细胞介导排斥反应（CMR；中位数：0.27%，IQR：0.19%-1.30%；P=0.01）患者相比，抗体介导排斥反应（ABMR）患者的 dd-cfDNA 百分比更高（中位数 1.35%，IQR：1.10%-1.90%）。dd-cfDNA 检测不能区分 CMR 患者和无排斥反应的患者。CMR 的 ROC 曲线下面积（AUC）为 0.42（95%CI：0.17-0.66）。对于 ABMR，AUC 为 0.82（95%CI：0.71-0.93），dd-cfDNA≥0.74%时，灵敏度为 100%，特异性为 71.8%，PPV 为 68.6%，NPV 为 100%。dd-cfDNA 检测不能区分肾移植受者的 CMR 与无排斥反应，尽管 ABMR 的鉴别性能更强。
