Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Erasmus MC, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Transplantation. 2022 Sep 1;106(9):1777-1786. doi: 10.1097/TP.0000000000004078. Epub 2022 Mar 10.
Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as a marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR indel method that allowed for the absolute quantification of ddcfDNA.
In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pretransplantation; at 3, 7, and 180 d after transplantation; and at time of for-cause biopsies obtained within the first 180 d after transplantation.
Median (interquartile range) ddcfDNA concentration was significantly higher on day 3 (58.3 [17.7-258.3] copies/mL) and day 7 (25.0 [10.4-70.8] copies/mL) than on day 180 after transplantation (4.2 [0.0-8.3] copies/mL; P < 0.001 and P < 0.001, respectively). At time of biopsy-proven AR (BPAR), between day 11 and day 180 after transplantation, ddcfDNA concentration was significantly higher (50.0 [25.0-108.3] copies/mL) than those when biopsies showed non-AR (0.0 [0.0-15.6] copies/mL; P < 0.05). ddcfDNA concentration within the first 10 d after transplantation showed no significant difference between recipients with BPAR and those with non-AR in their biopsy or between recipients with BPAR and ddcfDNA measured at day 3 and day 7.
Unfortunately, ddcfDNA concentration is not a good biomarker to detect AR within the first 10 d after transplantation; however, BPAR occurring after 10 d after transplantation can be detected in kidney transplant recipients by ddcfDNA using a novel and unique high-throughput droplet digital PCR indel method.
供体来源的无细胞 DNA（ddcfDNA）是一种很有前途的微创生物标志物，可用于检测肾移植受者的急性排斥反应（AR）。为了评估 ddcfDNA 作为 AR 标志物的诊断价值，使用一种新型高通量数字 PCR 插入缺失方法在肾移植后多个时间点定量检测 ddcfDNA，该方法允许对 ddcfDNA 进行绝对定量。
本研究分析了 223 例连续肾移植受者的血浆样本，在移植前；移植后 3、7 和 180 天；以及移植后 180 天内因原因进行活检时。
与移植后 180 天（4.2 [0.0-8.3] 拷贝/ml）相比，移植后 3 天（58.3 [17.7-258.3] 拷贝/ml）和 7 天（25.0 [10.4-70.8] 拷贝/ml）时的 ddcfDNA 浓度中位数（四分位距）显著升高（P<0.001 和 P<0.001）。在经活检证实的 AR（BPAR）时，即在移植后第 11 天至第 180 天之间，ddcfDNA 浓度（50.0 [25.0-108.3] 拷贝/ml）显著高于非 AR 活检时的浓度（0.0 [0.0-15.6] 拷贝/ml；P<0.05）。在移植后 10 天内，BPAR 受者与非 AR 受者的活检或与 3 天和 7 天的 ddcfDNA 测量值之间，ddcfDNA 浓度无显著差异。
不幸的是，ddcfDNA 浓度并不是检测移植后 10 天内 AR 的良好生物标志物；然而，使用新型独特的高通量数字 PCR 插入缺失方法，可以检测移植后 10 天以后的肾移植受者的 BPAR。
