供体细胞游离 DNA 对肾移植急性排斥反应治疗的动态反应。
Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts.
机构信息
CareDx, South San Francisco, California.
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
出版信息
Kidney360. 2021 Feb 3;2(4):729-736. doi: 10.34067/KID.0000042021. eCollection 2021 Apr 29.
BACKGROUND
The quantification of rejection treatment efficacy has been insufficient using traditional markers due, in part, to the lagging response of serum creatinine and histologic alterations on biopsy specimens. Donor-derived cell-free DNA (dd-cfDNA) is a molecular marker of injury that may assess allograft injury after rejection.
METHODS
Retrospective review of the DART study identified 70 patients who had a clinically indicated biopsy, simultaneous dd-cfDNA measurement, and at least one follow-up dd-cfDNA within 3 months post-treatment. Thirty-five patients had no biopsy-proven rejection and no rejection treatment (NR), 16 patients had no biopsy-proven rejection but did receive rejection treatment (CR), 9 patients had diagnosis of ABMR/mixed rejection on biopsy and received rejection treatment (ABMR), and 10 patients had diagnosis of TCMR and received rejection treatment (TCMR). The CR, ABMR, and TCMR groups combined to form a rejection (R) group.
RESULTS
In the R group, median dd-cfDNA values at baseline and 1 month were 0.62% and 0.35% (n=21 pairs, p=0.34), and at baseline and 2-3 months were 0.77% and 0.21% (n=23 pairs, p=0.002). In TCMR, median dd-cfDNA values at baseline and 1 month were 1.13% and 0.37% (n=5 pairs, p=0.63), and at baseline and 2-3 months were 0.25% and 0.12% (n=9 pairs, p=0.004). In ABMR, median dd-cfDNA values at baseline and 1 month were 1.61% and 1.2 % (n=6 pairs, p>0.99), and at baseline and 2-3 months were 3.85% and 1.32% (n=6 pairs, p=0.09). In CR, median dd-cfDNA values at baseline and 1 month were 0.31% and 0.29% (n=10 pairs, p=0.38), and at baseline and 2-3 months were 0.38% and 0.17% (n=8 pairs, p=0.31). Lastly, in NR, median dd-cfDNA values at baseline and 1 month were 0.23% and 0.18% (n=21 pairs, p=0.10), and at baseline and 2-3 months were 0.33% and 0.17% (n=26 pairs, p=0.003). Changes in serum creatinine across 1 month and 2-3 months following rejection were similar.
CONCLUSIONS
dd-cfDNA may be a useful dynamic biomarker to assess the health of the kidney allograft following rejection treatment.
背景
由于血清肌酐的滞后反应和活检标本的组织学改变，传统标志物对排斥反应治疗效果的量化一直不够充分。供体来源的无细胞 DNA（dd-cfDNA）是一种损伤的分子标志物，可在排斥反应后评估移植物损伤。
方法
对 DART 研究进行回顾性分析，确定了 70 名患者，他们进行了临床指征明确的活检，同时进行了 dd-cfDNA 测量，并在治疗后 3 个月内至少有一次后续 dd-cfDNA。35 名患者无活检证实的排斥反应且未接受排斥反应治疗（NR），16 名患者无活检证实的排斥反应但接受了排斥反应治疗（CR），9 名患者在活检中诊断为 ABMR/混合排斥反应并接受了排斥反应治疗（ABMR），10 名患者诊断为 TCMR 并接受了排斥反应治疗（TCMR）。CR、ABMR 和 TCMR 组联合形成排斥（R）组。
结果
在 R 组中，基线和 1 个月时的 dd-cfDNA 值中位数分别为 0.62%和 0.35%（n=21 对，p=0.34），基线和 2-3 个月时的 dd-cfDNA 值中位数分别为 0.77%和 0.21%（n=23 对，p=0.002）。在 TCMR 中，基线和 1 个月时的 dd-cfDNA 值中位数分别为 1.13%和 0.37%（n=5 对，p=0.63），基线和 2-3 个月时的 dd-cfDNA 值中位数分别为 0.25%和 0.12%（n=9 对，p=0.004）。在 ABMR 中，基线和 1 个月时的 dd-cfDNA 值中位数分别为 1.61%和 1.2%（n=6 对，p>0.99），基线和 2-3 个月时的 dd-cfDNA 值中位数分别为 3.85%和 1.32%（n=6 对，p=0.09）。在 CR 中，基线和 1 个月时的 dd-cfDNA 值中位数分别为 0.31%和 0.29%（n=10 对，p=0.38），基线和 2-3 个月时的 dd-cfDNA 值中位数分别为 0.38%和 0.17%（n=8 对，p=0.31）。最后，在 NR 中，基线和 1 个月时的 dd-cfDNA 值中位数分别为 0.23%和 0.18%（n=21 对，p=0.10），基线和 2-3 个月时的 dd-cfDNA 值中位数分别为 0.33%和 0.17%（n=26 对，p=0.003）。1 个月和 2-3 个月后血清肌酐的变化相似。
结论
dd-cfDNA 可能是一种有用的动态生物标志物，可用于评估排斥反应治疗后肾脏移植物的健康状况。
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