AbstractDrug repurposing in glomerular disease can deliver opportunities for steroid-free regimens, enable personalized multi-target options for resistant or relapsing disease and enhance treatment options for understudied populations (for example, children) and in resource-limited settings. Identification of drug-repurposing candidates can be data driven, which utilizes existing data on disease pathobiology, drug features and clinical outcomes, or experimental, which involves high-throughput drug screens.

摘要肾小球疾病的药物再利用可以为无类固醇方案提供机会，为耐药性或复发性疾病提供个性化的多靶点选择，并为研究不足的人群（例如儿童）和资源有限的环境提供更多的治疗选择。药物再利用候选者的鉴定可以是数据驱动的，其利用关于疾病病理生物学，药物特征和临床结果的现有数据，或者是涉及高通量药物筛选的实验数据。

Information from databases of approved drugs, clinical trials and PubMed registries suggests that at least 96 drugs on the market cover 49 targets with immunosuppressive potential that could be candidates for drug repurposing in glomerular disease. Furthermore, evidence to support drug repurposing is available for 191 immune drug target–glomerular disease pairs.

来自批准药物，临床试验和PubMed注册数据库的信息表明，市场上至少有96种药物涵盖49种具有免疫抑制潜力的靶标，这些靶标可能是肾小球疾病药物再利用的候选者。此外，支持药物再利用的证据可用于191种免疫药物-靶标-肾小球疾病对。

Non-immunological drug repurposing includes strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis. Recommended strategies to expand drug-repurposing capacity in glomerular disease include enriching drug databases with glomeruli-specific information, enhancing the accessibility of primary clinical trial data, biomarker discovery to improve participant selection into clinical trials and improve surrogate outcomes and initiatives to reduce patent, regulatory and organizational hurdles.Key points.

非免疫药物再利用包括减少血液动力学超负荷，足细胞损伤和肾纤维化的策略。扩大肾小球疾病药物再利用能力的推荐策略包括用肾小球特异性信息丰富药物数据库，增强主要临床试验数据的可及性，发现生物标志物以改善参与者对临床试验的选择，并改善替代结果和减少专利，监管和组织障碍的举措。关键点。

Drug repurposing can improve the treatment of glomerular disease by providing steroid-free regimens, enabling options for resistant or relapsing disease, enhancing treatment options for understudied populations and increasing therapy options in resource-limited settings.

药物再利用可以通过提供无类固醇方案，为耐药性或复发性疾病提供选择，增强未充分研究人群的治疗选择以及在资源有限的环境中增加治疗选择来改善肾小球疾病的治疗。

Contemporary methods of identifying drug-repurposing candidates can be data driven or experimental.

识别药物再利用候选者的当代方法可以是数据驱动的或实验性的。

At least 96 drugs on the market have targets with immunosuppressive potential that could be candidates for repurposing for glomerular disease treatment.

市场上至少有96种药物具有免疫抑制潜力，可能成为重新用于肾小球疾病治疗的候选药物。

Non-immunological drug repurposing for glomerular disease involves strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis.

用于肾小球疾病的非免疫药物再利用涉及减少血液动力学超负荷，足细胞损伤和肾纤维化的策略。

Strategies to expand drug-repurposing capacity need to enrich datasets with glomeruli-specific information, enhance the accessibility of clinical trial data, improve biomarker discovery and address patent, regulatory and organizational hurdles.

扩大药物再利用能力的策略需要用肾小球特异性信息丰富数据集，增强临床试验数据的可及性，改善生物标志物发现并解决专利，监管和组织障碍。

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Fig. 1: Methodologies for identifying candidate drugs for repurposing.Fig. 2: Drug classes targeting innate immune system and complement cascade for repurposing in glomerular disease.Fig. 3: Drug classes targeting adaptive immune system and downstream mechanisms for repurposing in glomerular disease.Fig.

图1：用于识别用于再利用的候选药物的方法。图2：针对先天免疫系统和补体级联的药物类别，用于肾小球疾病的再利用。。图。

4: Current evidence supporting drug target–glomerular disease pairs for drug repurposing..

4： 。。

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Frail, D. E. et al. Pioneering government-sponsored drug repositioning collaborations: progress and learning. Nat. Rev. Drug. Discov. 14, 833–841 (2015).Article

Frail，D.E.等人。开创性的政府资助的药物重新定位合作：进展和学习。Nat.Rev.Drug公司。迪斯科。14833-841（2015）。文章

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Download referencesAcknowledgementsM.S.Y.N. acknowledges support for the research of this work from the Royal Brisbane and Women’s Hospital Foundation (2020 Robert and Janelle Bird Postdoctoral Research Fellowship).Author informationAuthors and AffiliationsKidney Health Service, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, AustraliaMonica Suet Ying NgConjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, Queensland, AustraliaMonica Suet Ying NgFaculty of Medicine, The University of Queensland, Brisbane, Queensland, AustraliaMonica Suet Ying Ng & Ross S.

下载referencesAcknowledgementsM。S、 Y.N.感谢皇家布里斯班和妇女医院基金会（2020年罗伯特和珍妮尔·伯德博士后研究奖学金）对这项工作的研究的支持。作者信息作者和附属机构澳大利亚昆士兰布里斯班皇家布里斯班妇女医院Skidney Health Service，澳大利亚昆士兰布里斯班病理学昆士兰内科实验室，澳大利亚昆士兰布里斯班病理学昆士兰大学医学院，昆士兰布里斯班。

FrancisDepartment of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, Queensland, AustraliaMonica Suet Ying Ng, Ross S. Francis, Carmel M. Hawley & David W. JohnsonDepartment of Rheumatology, Saint Vincent’s Hospital, Sydney, New South Wales, AustraliaGursimran KaurSaint Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, AustraliaGursimran KaurRheumatology Department, Sunshine Coast University Hospital, Birtinya, Queensland, AustraliaGursimran KaurTranslational Research Institute, Brisbane, Queensland, AustraliaCarmel M.

弗朗西斯（Francis Department of Rental and Transplant Services），亚历山德拉公主医院（Princess Alexandra Hospital），澳大利亚昆士兰布里斯班（Australia Monica Suet Ying Ng），罗斯（Ross S.Francis），卡梅尔（Carmel M.Hawley）和大卫（David W.Johnson）新南威尔士州悉尼圣文森特医院风湿病科，澳大利亚新南威尔士州悉尼新南威尔士大学医学院RMEL M。

Hawley & David W. JohnsonCentre for Kidney Disease Research, University of Queensland, Brisbane, Queensland, AustraliaCarmel M. Hawley & David W. JohnsonAuthorsMonica Suet Ying NgView author publicationsYou can also search for this author in.

澳大利亚昆士兰布里斯班昆士兰大学霍利和大卫·W·约翰逊肾脏疾病研究中心Carmel M·霍利和大卫·W·约翰逊作者Monica Suet Ying NgView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarRoss S.FrancisView作者出版物您也可以在

PubMed Google ScholarCarmel M. HawleyView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsM.S.Y.N., G.K. and R.S.F. researched data for the article. M.S.Y.N. wrote the article. All authors made substantial contributions to discussions of the content, and reviewed or edited the manuscript before submission.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献。S、 Y.N.，G.K.和R.S.F.研究了这篇文章的数据。M、 S.Y.N.写了这篇文章。所有作者都对内容的讨论做出了重大贡献，并在提交前对稿件进行了审查或编辑。对应作者对应。

Monica Suet Ying Ng.Ethics declarations

Monica Suet Ying Ng。道德宣言

Competing interests

相互竞争的利益

M.S.Y.N. has received research grants and travel sponsorships from Avant Foundation and postdoctoral research fellowship from the Royal Brisbane and Women’s Hospital Foundation. G.K. has received research grants from the New Zealand Rheumatology Association. R.S.F. has received consultancy fees from Exelixis.

M、 S.Y.N.获得了先锋基金会的研究资助和旅行赞助，以及皇家布里斯班和妇女医院基金会的博士后研究奖学金。G、 K.获得了新西兰风湿病协会的研究资助。R、 S.F.已收到Exelixis的咨询费。

C.M.H. has received research grants from Baxter Healthcare. D.W.J. has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from Astra Zeneca, Bayer, and AWAK, speaker’s honoraria from Ono and Boehringer Ingelheim & Lilly, and travel sponsorships from Ono and Amgen; D.W.J.

C、 M.H.已获得Baxter Healthcare的研究资助。D、 W.J.获得了巴克斯特医疗保健公司和费森尤斯医疗保健公司的咨询费、研究补助金、演讲者酬金和旅行赞助，阿斯特拉·捷利康公司、拜耳公司和AWAK公司的咨询费，小野公司和勃林格殷格翰和礼来公司的演讲者酬金，以及小野公司和安进公司的旅行赞助；D、 W.J。

is a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant..

是澳大利亚国家健康与医学研究委员会领导力研究者资助的当前接受者。。

Peer review

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Peer review information

同行评审信息

Nature Reviews Nephrology thanks Gabriel Cara Fuentes, Duvuru Geetha, William Smoyer and Vladimir Tesar for their contribution to the peer review of this work.

《自然评论肾脏病学》感谢Gabriel Cara Fuentes，Duvuru Geetha，William Smoyer和Vladimir Tesar为这项工作的同行评审做出的贡献。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Related linksEuropean Medicines Agency: https://www.ema.europa.eu/en/medicinesNIH clinical trials database: https://www.clinicaltrials.gov/US Food and Drug Administration: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfmSupplementary informationSupplementary InformationGlossaryAdaptive trials.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。相关链接欧洲药品管理局：https://www.ema.europa.eu/en/medicinesNIH临床试验数据库：https://www.clinicaltrials.gov/UShttps://www.accessdata.fda.gov/scripts/cder/daf/index.cfmSupplementary信息补充信息词汇适应性试验。

Clinical trials that allow modifications to trial protocol after trial initiation without undermining internal validity. Adaptive trials move away from traditional phase I–III categories and allows a single study to move between different phases of clinical trials.

允许在试验开始后修改试验方案而不损害内部有效性的临床试验。适应性试验摆脱了传统的I-III期类别，允许一项研究在临床试验的不同阶段之间进行。

Bags-of-words

字里行间

A method of representing text data for natural language processing or machine-learning algorithms that converts text into an unordered collection of words; captures word frequency but not word order.

一种表示文本数据的方法，用于自然语言处理或机器学习算法，该算法将文本转换为无序的单词集合；捕获词频，但不捕获词序。

Basket trials

Clinical trials in which a drug is tested against multiple diseases with a shared disease mechanism (for example, testing an anti-complement drug against lupus nephritis, IgAN, membranous nephropathy, C3 glomerulopathy and dense deposit disease); also known as bucket trials.

临床试验，其中药物针对具有共同疾病机制的多种疾病进行测试（例如，测试针对狼疮性肾炎，IgAN，膜性肾病，C3肾小球病和致密沉积病的抗补体药物）；也称为桶试验。

First-pass metabolism

首过代谢

Pharmacological phenomenon whereby a drug undergoes metabolism prior to reaching systemic circulation or site of action. The first-pass effect is often associated with the liver, particularly for oral medications, but can also occur in the small intestine, lungs, vasculature or other metabolically active tissues..

药物在到达体循环或作用部位之前经历代谢的药理学现象。首过效应通常与肝脏有关，特别是口服药物，但也可能发生在小肠，肺，脉管系统或其他代谢活跃的组织中。。

Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleNg, M.S.Y., Kaur, G., Francis, R.S.

权利和许可Pringer Nature或其许可人（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文，M.S.Y.，Kaur，G.，Francis，R.S。

et al. Drug repurposing for glomerular diseases: an underutilized resource..

等。肾小球疾病的药物再利用：未充分利用的资源。。

Nat Rev Nephrol (2024). https://doi.org/10.1038/s41581-024-00864-8Download citationAccepted: 17 June 2024Published: 31 July 2024DOI: https://doi.org/10.1038/s41581-024-00864-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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