Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Clin Transplant. 2021 Sep;35(9):e14402. doi: 10.1111/ctr.14402. Epub 2021 Jul 14.
Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized.
We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA.
Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P < .0001).
Abnormalities in dd-cfDNA levels are associated with clinical parameters commonly used as surrogate endpoints for adverse allograft outcomes, raising the possibility that molecular injury as characterized by dd-cfDNA could help identify patients at risk of these outcomes.
供体来源的无细胞 DNA（dd-cfDNA）是移植受者同种异体损伤的标志物；然而，dd-cfDNA 与其他与不良同种异体结果相关的临床参数之间的关系尚未得到很好的描述。
我们对 DART 队列（ClinicalTrials.gov 标识符：NCT02424227）中的肾移植受者进行了回顾性分析，以评估 eGFR 下降、新出现的供体特异性抗体（dnDSA）和 dd-cfDNA 之间的关系。
在移植后第一年，dd-cfDNA 水平升高（≥1%）和 dd-cfDNA 变异性升高（≥.34%）与第二年 eGFR 下降≥25%相关（21.4%与 4.1%，P=.005；25%与 3.6%，P=.002）。与 DSA 阴性患者的样本相比，同时存在新出现 HLA-DSA 的患者样本中的 dd-cfDNA 水平更高（P<.0001）。
dd-cfDNA 水平异常与通常用作不良同种异体结果替代终点的临床参数相关，这表明 dd-cfDNA 所描述的分子损伤可能有助于识别有这些结果风险的患者。
