Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
CareDx, Inc, Brisbane, California, USA.
Clin Transplant. 2024 Nov;38(11):e70019. doi: 10.1111/ctr.70019.
Serial monitoring of dd-cfDNA and change from baseline can provide meaningful information beyond absolute thresholds. We describe dd-cfDNA trajectories from the baseline before and after acute rejection (AR) and de novo donor-specific antibodies (dnDSA) detection in kidney transplant recipients (KTRs).
We included KTR from 02/2019 to 03/2022 with serial dd-cfDNA. The primary analysis compared the time-varying change in dd-cfDNA from baseline in KTR first AR on biopsy [AR] to patients with no-AR on biopsy [no-AR].
151 KTR were analyzed (AR = 56 KTR, no-AR = 95 KTRs). In the AR group, dd-cfDNA rose ahead of diagnosis: median rise from baseline was 75% at -3 months, 32% at -2 months, and 325% at -1 month before biopsy. At the time of biopsy, the median rise in dd-cfDNA from baseline was 291% (IQR [interquartile range] 88%-1081%) in AR and 17% (IQR 0%- 194%) in no-AR (p < 0.0001). Following treatment, dd-cfDNA values fell in the AR group with a median change from baseline of 94.7% at +1 month, 10.5% at +2 months, and 0% at +3 months. These trajectories were not observed in the no-AR group. Similarly, there were no significant differences in eGFR (estimated glomerular filtration rate) trajectories between the two groups. The median change from baseline to dnDSA detection was 141% (IQR 112%-574%). In KTRs with persistent rejection, median dd-cfDNA was 0.95% (IQR 0.44-1.8) compared to 0.19% (IQR 0.12-0.31) in subjects with no rejection on follow-up (p < 0.001).
The significant changes from baseline observed before and after AR show how serial monitoring enhances dd-cfDNA utility and allows for earlier identification of evolving injury and monitoring treatment response.
连续监测 dd-cfDNA 并与基线相比变化可以提供超越绝对阈值的有意义信息。我们描述了肾移植受者（KTR）在急性排斥（AR）和新出现的供体特异性抗体（dnDSA）检测前后基线的 dd-cfDNA 轨迹。
我们纳入了 2019 年 2 月至 2022 年 3 月进行连续 dd-cfDNA 检测的 KTR。主要分析比较了首次活检 AR 的 KTR（AR 组）和无活检 AR 的 KTR（无 AR 组）的基线 dd-cfDNA 时变变化。
分析了 151 例 KTR（AR 组 56 例，无 AR 组 95 例）。在 AR 组中，dd-cfDNA 在诊断前升高：活检前-3 个月时基线上升中位数为 75%，-2 个月时为 32%，-1 个月时为 325%。在活检时，AR 组中，dd-cfDNA 从基线的中位数升高 291%（IQR [四分位间距] 88%-1081%），无 AR 组为 17%（IQR 0%-194%）（p<0.0001）。在接受治疗后，AR 组的 dd-cfDNA 值下降，+1 个月时从基线的中位数变化为 94.7%，+2 个月时为 10.5%，+3 个月时为 0%。在无 AR 组中未观察到这些轨迹。同样，两组间 eGFR（肾小球滤过率估计值）轨迹无显著差异。从基线到 dnDSA 检测的中位数变化为 141%（IQR 112%-574%）。在持续排斥的 KTR 中，中位 dd-cfDNA 为 0.95%（IQR 0.44-1.8），而在随访中无排斥的患者中为 0.19%（IQR 0.12-0.31）（p<0.001）。
在 AR 前后观察到的与基线相比的显著变化表明，连续监测如何增强 dd-cfDNA 的效用，并允许更早地识别进行性损伤和监测治疗反应。
