用 CSL346 阻断血管内皮生长因子 (VEGF)-B 治疗糖尿病肾病:2A 期随机对照试验。

IF 10.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2024-08-16 DOI:10.1681/ASN.0000000000000438
Melisa Cooper, David Z I Cherney, Tom H Greene, Hiddo J L Heerspink, Meg Jardine, Julia B Lewis, Muh Geot Wong, Elbalejandra Baquero, Mark Heise, Jeanine Jochems, Diana Lanchoney, Charles Liss, David Reiser, Pierre Scotney, Elena Velkoska, Jamie P Dwyer
{"title":"用 CSL346 阻断血管内皮生长因子 (VEGF)-B 治疗糖尿病肾病:2A 期随机对照试验。","authors":"Melisa Cooper, David Z I Cherney, Tom H Greene, Hiddo J L Heerspink, Meg Jardine, Julia B Lewis, Muh Geot Wong, Elbalejandra Baquero, Mark Heise, Jeanine Jochems, Diana Lanchoney, Charles Liss, David Reiser, Pierre Scotney, Elena Velkoska, Jamie P Dwyer","doi":"10.1681/ASN.0000000000000438","DOIUrl":null,"url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":10.3000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Vascular Endothelial Growth Factor-B Blockade with CSL346 in Diabetic Kidney Disease: A Phase 2A Randomized Controlled Trial.\",\"authors\":\"Melisa Cooper, David Z I Cherney, Tom H Greene, Hiddo J L Heerspink, Meg Jardine, Julia B Lewis, Muh Geot Wong, Elbalejandra Baquero, Mark Heise, Jeanine Jochems, Diana Lanchoney, Charles Liss, David Reiser, Pierre Scotney, Elena Velkoska, Jamie P Dwyer\",\"doi\":\"10.1681/ASN.0000000000000438\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\",\"PeriodicalId\":17217,\"journal\":{\"name\":\"Journal of The American Society of Nephrology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.3000,\"publicationDate\":\"2024-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of The American Society of Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1681/ASN.0000000000000438\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of The American Society of Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1681/ASN.0000000000000438","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:糖尿病肾病(DKD)患者血管内皮生长因子 B(VEGF-B)表达的增加与肾小球荚膜细胞中脂质沉积的增加有关。使用抗血管内皮生长因子 B 抗体降低糖尿病肾病动物模型中血管内皮生长因子 B 的活性可改善肾小球损伤的组织学证据并降低白蛋白尿;其效果归因于防止肾脏中异位脂质沉积。CSL346 是一种新型人源化单克隆抗体,能与血管内皮生长因子-B 高亲和力结合。针对 2 型糖尿病患者的血管内皮生长因子-B 可改善 DKD 进展指标:一项国际随机、双盲、安慰剂对照 2a 期研究(NCT04419467)评估了 CSL346(8 mg/kg 或 16 mg/kg,每 4 周皮下注射一次,共 12 周)对尿白蛋白与肌酐比值 (UACR) ≥150 mg/g (17.0 mg/mmol)、eGFR >20 mL/min/1.73m2 的 2 型糖尿病患者的疗效。对 CSL346 的疗效、安全性/耐受性、药代动力学和药效学进行了评估。主要分析比较了两个 CSL346 剂量组与安慰剂组在第 16 周时 UACR 对数变换后与基线相比的变化:结果:共有 114 人接受了随机治疗。与安慰剂相比,第 16 周时 CSL346 并未明显降低 UACR(CSL346 组合组与安慰剂的差异 95% 置信区间]:4.0% [-14.7, 26.8]).此外,在参试者亚组(肾功能损害程度或使用钠-葡萄糖共转运体 2 [SGLT2] 抑制剂)或反映近端肾小管损伤的尿液生物标志物方面均未见效果。CSL346 的耐受性总体良好;但从第 2 周开始,CSL346 16 mg/kg 与安慰剂相比,舒张压显著升高,差异范围为 +3.8 至 +5.3 mmHg(第 16 周时,P = 0.002):结论:与安慰剂相比,CSL346 在 16 周时并不能降低 2 型糖尿病和 DKD 参与者的 UACR,而且与舒张压升高有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Vascular Endothelial Growth Factor-B Blockade with CSL346 in Diabetic Kidney Disease: A Phase 2A Randomized Controlled Trial.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
期刊最新文献
Authors' Reply: Utility of Urinary CD4 + T-Cell Count in Detecting ANCA-Associated Vasculitis Renal Relapse. Glomerular Endothelial Cell Receptor Adhesion G-Protein-Coupled Receptor F5 (ADGRF5) and the Integrity of the Glomerular Filtration Barrier. P2Y2R and Cyst Growth in Polycystic Kidney Disease. The Plasma Metabolome and Risk of Incident Kidney Stones. Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1