Donor-derived Cell-free DNA as a Noninvasive Biomarker of Kidney Allograft Rejection in Pediatric Kidney Transplantation.

IF 5.3 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2025-04-09 DOI:10.1097/TP.0000000000005403

Julien Hogan, Roshan George, Carissa Hayes, Olivier Aubert, Véronique Baudouin, Elodie Cheyssac, Charlotte Duneton, Chris Fan, Margret Kamel, Marion Rabant, Hong Yin, Alexandre Loupy, Rouba Garro

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引用次数: 0

Abstract

Background: Allograft biopsy remains the gold standard to diagnose rejection. New noninvasive biomarkers are needed to avoid unnecessary biopsies and to diagnose early rejection. We studied the performance of donor derived cell-free DNA (dd-cfDNA) to detect rejection in an unselected cohort of pediatric kidney transplant recipients (pKTRs) and determined whether dd-cfDNA could improve standard-of-care monitoring and detection of kidney allograft rejection in children.

Methods: We included 196 pKTRs, who underwent 367 biopsies with concomitant dd-cfDNA assessment. We assessed the association of dd-cfDNA with histological lesions and with rejection using a Cox regression model and compared the discrimination of 3 models: standard of care, dd-cfDNA alone, and combined.

Results: We found a significant increase in dd-cfDNA levels with higher degree of inflammation on the biopsies. dd-cfDNA was strongly and independently associated with the presence of allograft rejection (odds ratio 1.89, 95% confidence interval [CI], 1.40-2.60). dd-cfDNA alone had a fair discrimination of 0.76 (95% CI, 0.69-0.81) to detect rejection and its addition to standard of care resulted in a significant increase in discrimination from 0.80 (95% CI, 0.71-0.85) to 0.84 (95% CI, 0.79-0.90), P = 0.01.

Conclusions: dd-cfDNA combined with standard of care improves the prediction of rejection in pKTRs. Further specific studies are needed to better define how to use this promising biomarker in various contexts of use in children.

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供体来源的无细胞DNA作为儿童肾移植排斥反应的无创生物标志物。

背景：同种异体移植活检仍然是诊断排斥反应的金标准。需要新的无创生物标志物来避免不必要的活检和诊断早期排斥反应。我们研究了供体来源无细胞DNA （dd-cfDNA）检测儿童肾移植受者（pKTRs）排斥反应的性能，并确定dd-cfDNA是否可以改善儿童肾移植排斥反应的标准监测和检测。方法：我们纳入了196名pktr患者，进行了367次活检，并进行了dd-cfDNA评估。我们使用Cox回归模型评估了dd-cfDNA与组织学病变和排斥反应的关系，并比较了标准治疗、单独使用dd-cfDNA和联合使用dd-cfDNA 3种模型的区别。结果：我们在活检中发现dd-cfDNA水平显著增加，炎症程度较高。dd-cfDNA与同种异体移植排斥反应存在强烈且独立的相关性（优势比1.89,95%可信区间[CI]， 1.40-2.60）。单独使用dd-cfDNA检测排斥反应的公平判别率为0.76 (95% CI, 0.69-0.81)，将其加入标准护理后，判别率从0.80 （95% CI, 0.71-0.85）显著增加到0.84 (95% CI, 0.79-0.90), P = 0.01。结论：dd-cfDNA联合标准护理可提高pktr排斥反应的预测。需要进一步的具体研究来更好地定义如何在各种儿童使用环境中使用这种有前途的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.