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稳定的肾移植(KTx)患者供体来源的无细胞 DNA(dd-cfDNA)的纵向变异受供体/受者变量的影响。

Longitudinal variance of Donor-Derived Cell-Free DNA (dd-cfDNA) in Stable Kidney Transplant (KTx) patients are influenced by donor/recipient variables.

机构信息

Intermountain Medical Center, Transplant Services, Murray, Utah, USA.

出版信息

Clin Transplant. 2021 Sep;35(9):e14395. doi: 10.1111/ctr.14395. Epub 2021 Jul 4.

DOI:10.1111/ctr.14395
PMID:34165192
Abstract

BACKGROUND

The longitudinal time-course of dd-cfDNA after kidney transplant (KTx) is not well-described. The cut off values of dd-cfDNA in KTx derive from biopsy-coupled single measurements. Meaningful interpretation necessitates understanding of: (1) time variance of dd-cfDNA levels post-KTx, (2) factors determining biologic variability, and (3) relationship to donor and recipient characteristics. We hypothesized that an understanding of the aforementioned factors would better inform clinical decision-making using dd-cfDNA.

METHODS

One hundred and twenty five KTx patients with dd-cfDNA obtained longitudinally were included. Univariate analyses were directed at inter-patient variability and intra-patient inter-occasion variability of dd-cfDNA. Multivariate linear regression was used in analyses accounting for repeat measures.

RESULTS

At 1-month post KTx median dd-cfDNA: (1) were higher in repeat KTx (.57%, P < .001), and dual KTx (1.10%, P = ns) versus a first KTx (.31%); (2) showed a significant difference in donor after cardiac death (DCD [.45%]) versus living related (LRD [.27%]) donors (P = .036). Longitudinal (1-3 months) dd-cfDNA measurements showed a significant downtrend for all donor types. Panel-reactive antibodies (PRA) were positively correlated with dd-cfDNA.

CONCLUSIONS

Repeat Tx, dual Tx, DCD, and PRA are associated with a higher dd-cfDNA. Incorporation of donor/recipient variables and time down post transplant is material for rational interpretation of dd-cfDNA.

摘要

背景

肾移植(KTx)后 dd-cfDNA 的纵向时间过程尚不清楚。KTx 中 dd-cfDNA 的截止值来自活检相关的单次测量。有意义的解释需要了解:(1)KTx 后 dd-cfDNA 水平的时间变化,(2)决定生物学变异性的因素,以及(3)与供体和受体特征的关系。我们假设,对上述因素的理解将更好地为使用 dd-cfDNA 做出临床决策提供信息。

方法

纳入 125 例接受 dd-cfDNA 纵向检测的 KTx 患者。单变量分析针对 dd-cfDNA 的个体间变异性和个体内不同时间点的变异性。使用多变量线性回归分析考虑重复测量。

结果

KTx 后 1 个月时,中位数 dd-cfDNA:(1)在重复 KTx(.57%,P<.001)和双 KTx(1.10%,P=ns)中高于首次 KTx(.31%);(2)在心脏死亡后供体(DCD [.45%])与活体相关供体(LRD [.27%])之间存在显著差异(P=.036)。所有供体类型的纵向(1-3 个月)dd-cfDNA 测量均呈显著下降趋势。面板反应性抗体(PRA)与 dd-cfDNA 呈正相关。

结论

重复 Tx、双 Tx、DCD 和 PRA 与较高的 dd-cfDNA 相关。纳入供体/受体变量和移植后时间的下降是合理解释 dd-cfDNA 的重要因素。

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