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用于肾移植患者非侵入性监测的液体活检

Liquid biopsy for non-invasive monitoring of patients with kidney transplants.

作者信息

Nassar Anthony, Cashman Katharine, Rao Shreya, Dagher Maribel, O'Brien Connor, Afif John, Cravedi Paolo, Azzi Jamil R

机构信息

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, MA, United States.

Division of Nephrology, Department of Medicine, Translational Transplant Research Center, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

出版信息

Front Transplant. 2023 Jun 8;2:1148725. doi: 10.3389/frtra.2023.1148725. eCollection 2023.

DOI:10.3389/frtra.2023.1148725
PMID:38993899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11235308/
Abstract

The current tools for diagnosing and monitoring native kidney diseases as well as allograft rejection in transplant patients are suboptimal. Creatinine and proteinuria are non-specific and poorly sensitive markers of injury. Tissue biopsies are invasive and carry potential complications. In this article, we overview the different techniques of liquid biopsy and discuss their potential to improve patients' kidney health. Several diagnostic, predictive, and prognostic biomarkers have been identified with the ability to detect and monitor the activity of native kidney diseases as well as early and chronic allograft rejection, such as donor-derived cell-free DNA, exosomes, messenger RNA/microsomal RNA, proteomics, and so on. While the results are encouraging, additional research is still needed as no biomarker appears to be perfect for a routine application in clinical practice. Despite promising advancements in biomarkers, the most important issue is the lack of standardized pre-analytical criteria. Large validation studies and uniformed standard operating procedures are required to move the findings from bench to bedside. Establishing consortia such as the Liquid Biopsy Consortium for Kidney Diseases can help expedite the research process, allow large studies to establish standardized procedures, and improve the management and outcomes of kidney diseases and of kidney transplant recipients.

摘要

目前用于诊断和监测移植患者的自身肾脏疾病以及同种异体移植排斥反应的工具并不理想。肌酐和蛋白尿是损伤的非特异性且敏感性较差的标志物。组织活检具有侵入性且存在潜在并发症。在本文中,我们概述了液体活检的不同技术,并讨论了它们改善患者肾脏健康的潜力。已经鉴定出几种诊断、预测和预后生物标志物,它们能够检测和监测自身肾脏疾病的活动以及早期和慢性同种异体移植排斥反应,例如供体来源的游离DNA、外泌体、信使RNA/微小RNA、蛋白质组学等。虽然结果令人鼓舞,但仍需要更多研究,因为似乎没有一种生物标志物在临床实践中的常规应用中是完美的。尽管生物标志物取得了有前景的进展,但最重要的问题是缺乏标准化的分析前标准。需要进行大型验证研究和统一的标准操作程序,以便将研究结果从实验室应用到临床。建立诸如肾脏疾病液体活检联盟这样的联合体有助于加快研究进程,使大型研究能够建立标准化程序,并改善肾脏疾病和肾移植受者患者的管理及治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c3/11235308/baf5df36c3d1/frtra-02-1148725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c3/11235308/baf5df36c3d1/frtra-02-1148725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c3/11235308/baf5df36c3d1/frtra-02-1148725-g001.jpg

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Liquid Biopsy: A New Avenue for the Diagnosis of Kidney Disease: Diabetic Kidney Disease, Renal Cancer, and IgA Nephropathy.液体活检:肾脏病诊断的新途径:糖尿病肾病、肾癌和 IgA 肾病。
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本文引用的文献

1
The Current State of Donor-Derived Cell-Free DNA Use in Allograft Monitoring in Kidney Transplantation.肾移植中供体来源游离DNA在同种异体移植监测中的应用现状
J Pers Med. 2022 Oct 12;12(10):1700. doi: 10.3390/jpm12101700.
2
Novel Biomarkers in Kidney Transplantation.肾脏移植中的新型生物标志物。
Semin Nephrol. 2022 Jan;42(1):2-13. doi: 10.1016/j.semnephrol.2022.01.007.
3
Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts.供体细胞游离 DNA 对肾移植急性排斥反应治疗的动态反应。
Kidney360. 2021 Feb 3;2(4):729-736. doi: 10.34067/KID.0000042021. eCollection 2021 Apr 29.
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Urinary mi-106a for the diagnosis of IgA nephropathy: Liquid biopsy for kidney disease.尿 miR-106a 诊断 IgA 肾病:肾脏疾病的液体活检。
Clin Chim Acta. 2022 May 1;530:81-86. doi: 10.1016/j.cca.2022.03.006. Epub 2022 Mar 9.
5
Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology.在微小病变性肾病中发现针对 Nephrin 的自身抗体支持新的自身免疫病因。
J Am Soc Nephrol. 2022 Jan;33(1):238-252. doi: 10.1681/ASN.2021060794. Epub 2021 Nov 3.
6
Exosomes: Emerging Therapy Delivery Tools and Biomarkers for Kidney Diseases.外泌体:用于肾脏疾病的新兴治疗递送工具和生物标志物
Stem Cells Int. 2021 Aug 21;2021:7844455. doi: 10.1155/2021/7844455. eCollection 2021.
7
Beyond the Biopsy: Monitoring Immune Status in Kidney Recipients.超越活检:监测肾移植受者的免疫状态。
Clin J Am Soc Nephrol. 2021 Sep;16(9):1413-1422. doi: 10.2215/CJN.14840920. Epub 2021 Aug 6.
8
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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Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy.自身抗体在膜性肾病的诊断、监测和治疗中的作用。
Front Immunol. 2021 Mar 22;12:593288. doi: 10.3389/fimmu.2021.593288. eCollection 2021.
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Liquid Biopsy: From Discovery to Clinical Application.液体活检:从发现到临床应用。
Cancer Discov. 2021 Apr;11(4):858-873. doi: 10.1158/2159-8290.CD-20-1311.