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肾移植后长达一年影响供体来源游离DNA水平的因素鉴定

Identification of Factors Influencing Donor-Derived Cell-Free DNA Levels up to One Year After Kidney Transplant.

作者信息

Mirza Ahmad, Gani Imran, Parvez Imran, Weaver Cari, Mulloy Laura, Kapoor Rajan

机构信息

Medical College of Georgia, Augusta University Hospital and Medical Center, 1120 15th Street, Augusta AD 3401, Georgia.

出版信息

J Transplant. 2024 Dec 31;2024:7673476. doi: 10.1155/joot/7673476. eCollection 2024.

DOI:10.1155/joot/7673476
PMID:39781105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11707014/
Abstract

Donor-derived cell-free DNA (dd-cfDNA) in the peripheral blood of allograft recipients has shown to early identify allograft injury. In this study, we assessed the factors that influence the amount of circulating dd-cfDNA during the first month postkidney transplant as well as its longitudinal trend. A consecutive series of 98 adult kidney transplant recipients at a single center between July 2018 and January 2020 were included in this study. All demographic and operative details were collected for donors and recipients of the organ transplant. Median eGFR, dd-cfDNA, and serum creatinine were calculated at 1, 2, 3, 6, and 12 month posttransplant. Descriptive statistics were used for patient demographics. Nonparametric comparisons of dd-cfDNA cumulative distributions between dichotomized groupings were evaluated using Kruskal-Wallis or Mann-Whitney tests. The median age of recipients was 54.5 years (IQR: 42.7-62.2). The cause of ESRD among recipients was hypertension (43%) and Type II diabetes mellitus (29%). Eighty-two percentage of patients received a deceased donor allograft, 14% received a living unrelated allograft, and 4% received a living related allograft. Sixteen percentage of recipients experienced delayed graft function (DGF). Median creatinine level at 1 month posttransplant was 1.75 mg/dL (IQR: 1.34-2.26) and median eGFR at 1 month posttransplant was 49.6 mL/min/1.73 m (IQR: 35-65). The median dd-cfDNA score at 1 month posttransplant for all recipients was 0.4% (IQR: 0.15-5.3). Donor sex was a statistically significant differential for dd-cfDNA score. Recipients from male donors had a significantly higher median dd-cf DNA score at 1 month posttransplant versus those who received a female kidney (0.57% vs. 0.28%, < 0.01). Highest median score was recorded at the first month posttransplant (0.4%, IQR: 0.26-0.74), and a sustained downward trend was observed through Month 2 (0.19%, IQR: 0.17-0.31) and Month 3 (0.19%, IQR: 0.15-0.26). Correlation between 1-, 2-, 3-, 6-, and 12-month posttransplant median dd-cfDNA scores between deceased donor and living donor (LRD and LURD) cohorts was not statistically significant. This study provides further insight into donor and recipient variables' effects on dd-cfDNA in the early posttransplant phase by analyzing a more diverse cohort of patients and adds to the knowledge around interpreting dd-cfDNA scores with clinical correlation for posttransplant management.

摘要

同种异体移植受者外周血中的供体来源游离DNA(dd-cfDNA)已被证明可早期识别同种异体移植损伤。在本研究中,我们评估了肾移植术后第一个月内影响循环dd-cfDNA量的因素及其纵向变化趋势。本研究纳入了2018年7月至2020年1月期间在单中心连续收治的98例成年肾移植受者。收集了器官移植供体和受体的所有人口统计学和手术细节。分别在移植后1、2、3、6和12个月计算估算肾小球滤过率(eGFR)、dd-cfDNA和血清肌酐的中位数。采用描述性统计分析患者人口统计学特征。使用Kruskal-Wallis检验或Mann-Whitney检验对二分分组之间的dd-cfDNA累积分布进行非参数比较。受者的中位年龄为54.5岁(四分位间距:42.7-62.2)。受者中终末期肾病的病因是高血压(43%)和II型糖尿病(29%)。82%的患者接受了死体供肾移植,14%接受了非亲属活体供肾移植,4%接受了亲属活体供肾移植。16%的受者发生了移植肾功能延迟恢复(DGF)。移植后1个月时肌酐水平中位数为1.75mg/dL(四分位间距:1.34-2.26),移植后1个月时eGFR中位数为49.6mL/min/1.73m²(四分位间距:35-65)。所有受者移植后1个月时dd-cfDNA分数中位数为0.4%(四分位间距:0.15-5.3)。供体性别对dd-cfDNA分数有统计学显著差异。与接受女性供肾的受者相比,接受男性供肾的受者在移植后1个月时dd-cfDNA分数中位数显著更高(0.57%对0.28%,P<0.01)。移植后第一个月记录到最高中位数分数(0.4%,四分位间距:0.26-0.74),并且在第2个月(0.19%,四分位间距:0.17-0.31)和第3个月(0.19%,四分位间距:0.15-0.26)观察到持续下降趋势。死体供肾组与活体供肾组(亲属活体供肾和非亲属活体供肾)在移植后1、2、3、6和12个月时的dd-cfDNA分数中位数之间的相关性无统计学意义。本研究通过分析更多样化的患者队列,进一步深入了解了供体和受体变量在移植后早期对dd-cfDNA的影响,并增加了有关将dd-cfDNA分数与临床相关性用于移植后管理解读的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/915ef2393f02/JTRANS2024-7673476.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/9db47086601f/JTRANS2024-7673476.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/686cd7eee07e/JTRANS2024-7673476.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/4a372993ad40/JTRANS2024-7673476.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/915ef2393f02/JTRANS2024-7673476.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/9db47086601f/JTRANS2024-7673476.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/686cd7eee07e/JTRANS2024-7673476.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/4a372993ad40/JTRANS2024-7673476.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbb/11707014/915ef2393f02/JTRANS2024-7673476.004.jpg

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本文引用的文献

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The Role of Donor Sex in Females Undergoing Repeat Kidney Transplant: Does Prior Donor Sex Matter?供体性别在接受再次肾移植的女性中的作用:既往供体性别是否重要?
Transplant Direct. 2022 Jul 15;8(8):e1352. doi: 10.1097/TXD.0000000000001352. eCollection 2022 Aug.
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Reconsidering Donor Race in Predicting Allograft and Patient Survival Among Kidney Transplant Recipients.重新考虑供者种族对肾移植受者移植肾和患者生存的预测作用。
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Donor-derived Cell-free DNA as a Graft Injury Marker Following Kidney Transplantation.
肾移植后供体来源的游离DNA作为移植损伤标志物
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Longitudinal variance of Donor-Derived Cell-Free DNA (dd-cfDNA) in Stable Kidney Transplant (KTx) patients are influenced by donor/recipient variables.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。
Clin Transplant. 2021 Sep;35(9):e14395. doi: 10.1111/ctr.14395. Epub 2021 Jul 4.
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Liquid biopsies: donor-derived cell-free DNA for the detection of kidney allograft injury.液体活检:用于检测肾移植损伤的供体游离 DNA。
Nat Rev Nephrol. 2021 Sep;17(9):591-603. doi: 10.1038/s41581-021-00428-0. Epub 2021 May 24.
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Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force.重新评估种族因素在肾脏病诊断中的纳入问题:NKF-ASN 工作组的中期报告。
J Am Soc Nephrol. 2021 Jun 1;32(6):1305-1317. doi: 10.1681/ASN.2021010039. Epub 2021 Apr 9.
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Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications.肾移植受者中供体来源游离DNA的生物学变异:临床意义
J Appl Lab Med. 2017 Nov 1;2(3):309-321. doi: 10.1373/jalm.2016.022731.
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OPTN/SRTR 2019 Annual Data Report: Kidney.OPTN/SRTR 2019 年度数据报告:肾脏。
Am J Transplant. 2021 Feb;21 Suppl 2:21-137. doi: 10.1111/ajt.16502.