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一项评估移植肾纤维化的定量超声人体首次研究。

A first-in-human study of quantitative ultrasound to assess transplant kidney fibrosis.

作者信息

Hysi Eno, Baek Jihye, Koven Alexander, He Xiaolin, Ulloa Severino Luisa, Wu Yiting, Kek Kendrix, Huang Shukai, Krizova Adriana, Farcas Monica, Ordon Michael, Fok Kai-Ho, Stewart Robert, Pace Kenneth T, Kolios Michael C, Parker Kevin J, Yuen Darren A

机构信息

Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.

出版信息

Nat Med. 2025 Mar;31(3):970-978. doi: 10.1038/s41591-024-03417-5. Epub 2025 Mar 3.

DOI:10.1038/s41591-024-03417-5
PMID:40033112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11922760/
Abstract

Kidney transplantation is the optimal treatment for renal failure. In the United States, a biopsy at the time of organ procurement is often used to assess kidney quality to decide whether it should be used for transplant. This assessment is focused on renal fibrotic burden, because fibrosis is an important measure of irreversible kidney injury. Unfortunately, biopsy at the time of transplant is plagued by problems, including bleeding risk, inaccuracies introduced by sampling bias and rapid sample preparation, and the need for round-the-clock pathology expertise. We developed a quantitative algorithm, called renal H-scan, that can be added to standard ultrasound workflows to quickly and noninvasively measure renal fibrotic burden in preclinical animal models and human transplant kidneys. Furthermore, we provide evidence that biopsy-based fibrosis estimates, because of their highly localized nature, are inaccurate measures of whole-kidney fibrotic burden and do not associate with kidney function post-transplant. In contrast, we show that whole-kidney H-scan fibrosis estimates associate closely with post-transplant renal function. Taken together, our data suggest that the addition of H-scan to standard ultrasound workflows could provide a safe, rapid and easy-to-perform method for accurate quantification of transplant kidney fibrotic burden, and thus better prediction of post-transplant renal outcomes.

摘要

肾移植是肾衰竭的最佳治疗方法。在美国,器官获取时的活检常被用于评估肾脏质量,以决定是否应将其用于移植。这种评估侧重于肾纤维化负担,因为纤维化是不可逆肾损伤的一项重要指标。不幸的是,移植时的活检存在诸多问题,包括出血风险、采样偏差和快速样本制备导致的不准确,以及对全天候病理专业知识的需求。我们开发了一种名为肾脏H扫描的定量算法,可添加到标准超声工作流程中,以快速、无创地测量临床前动物模型和人类移植肾脏的肾纤维化负担。此外,我们提供的证据表明,基于活检的纤维化评估因其高度局部化的性质,是对全肾纤维化负担的不准确测量,且与移植后肾功能无关。相比之下,我们表明全肾H扫描纤维化评估与移植后肾功能密切相关。综上所述,我们的数据表明,在标准超声工作流程中添加H扫描可为准确量化移植肾纤维化负担提供一种安全、快速且易于执行的方法,从而更好地预测移植后肾脏结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/11922760/53cc77fd4136/41591_2024_3417_Fig9_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/11922760/b442f7e67c51/41591_2024_3417_Fig5_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/11922760/77067a87b7c3/41591_2024_3417_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/11922760/2fbd511138cd/41591_2024_3417_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b0/11922760/2a2845c4c716/41591_2024_3417_Fig8_ESM.jpg
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Kidney Int Rep. 2022 Mar 28;7(6):1268-1277. doi: 10.1016/j.ekir.2022.03.021. eCollection 2022 Jun.
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Sci Transl Med. 2022 Mar 23;14(637):eaaz4028. doi: 10.1126/scitranslmed.aaz4028.
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Myofibroblast YAP/TAZ activation is a key step in organ fibrogenesis.肌成纤维细胞 YAP/TAZ 的激活是器官纤维化形成的关键步骤。
JCI Insight. 2022 Feb 22;7(4):e146243. doi: 10.1172/jci.insight.146243.
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