急性肾损伤：当前临床试验中的新兴药物治疗法。
Acute kidney injury: emerging pharmacotherapies in current clinical trials.
机构信息
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7022, Cincinnati, OH, 45229-3039, USA.
出版信息
Pediatr Nephrol. 2018 May;33(5):779-787. doi: 10.1007/s00467-017-3695-3. Epub 2017 Jun 10.
Abstract
Acute kidney injury (AKI) is a significant source of morbidity and mortality in pediatric patients, affecting more than one quarter of critically ill children. Despite significant need, there are no targeted therapies to reliably prevent or treat AKI. Recent advances in our understanding of renal injury and repair signaling pathways have enabled the development of several targeted pharmaceuticals. Here we review emerging pharmacotherapies for AKI that are currently in clinical trials. Categorized by their general mechanism of action, the therapies discussed include anti-inflammatory agents (recAP, AB103, ABT-719), antioxidants (iron chelators, heme arginate), vasodilators (levosimendan), apoptosis inhibitors (QPI-1002), and repair agents (THR-184, BB-3, mesenchymal stem cells).
摘要
急性肾损伤（AKI）是儿科患者发病率和死亡率的重要来源，超过四分之一的危重症儿童受其影响。尽管有巨大的需求，但目前尚无可靠的预防或治疗 AKI 的靶向疗法。我们对肾损伤和修复信号通路的理解的最新进展使几种靶向药物得以开发。在这里，我们综述了目前正在临床试验中的 AKI 的新兴药物治疗方法。根据其一般作用机制，讨论的治疗方法包括抗炎药（recAP、AB103、ABT-719）、抗氧化剂（铁螯合剂、精氨酸组血红素）、血管扩张剂（左西孟旦）、凋亡抑制剂（QPI-1002）和修复剂（THR-184、BB-3、间充质干细胞）。
相似文献
1
Acute kidney injury: emerging pharmacotherapies in current clinical trials.急性肾损伤：当前临床试验中的新兴药物治疗法。
Pediatr Nephrol. 2018 May;33(5):779-787. doi: 10.1007/s00467-017-3695-3. Epub 2017 Jun 10.
2
Recent early clinical drug development for acute kidney injury.急性肾损伤的近期早期临床药物研发
Expert Opin Investig Drugs. 2017 Feb;26(2):141-154. doi: 10.1080/13543784.2017.1274730. Epub 2016 Dec 27.
3
Drugs in Development for Acute Kidney Injury.急性肾损伤治疗药物的研发进展
Drugs. 2019 Jun;79(8):811-821. doi: 10.1007/s40265-019-01119-8.
4
Advances in pharmacotherapy for acute kidney injury.急性肾损伤药物治疗的进展
Expert Opin Pharmacother. 2022 Apr;23(6):713-726. doi: 10.1080/14656566.2022.2050214. Epub 2022 Mar 14.
5
Therapeutic strategies to prevent contrast-induced acute kidney injury.防治对比剂诱导急性肾损伤的治疗策略。
Curr Opin Cardiol. 2013 Nov;28(6):676-82. doi: 10.1097/HCO.0b013e3283653f41.
6
New drugs for acute kidney injury.急性肾损伤的新药。
Curr Opin Crit Care. 2020 Dec;26(6):525-535. doi: 10.1097/MCC.0000000000000778.
7
Milrinone Dosing Issues in Critically Ill Children With Kidney Injury: A Review.危重症肾损伤儿童米力农的给药问题：综述
J Cardiovasc Pharmacol. 2016 Feb;67(2):175-81. doi: 10.1097/FJC.0000000000000327.
8
Acute Kidney Injury in the Critically Ill Patient: A Current Review of the Literature.危重症患者的急性肾损伤：文献综述
J Intensive Care Med. 2016 Jun;31(5):319-24. doi: 10.1177/0885066615575699. Epub 2015 Mar 9.
9
Immunopathogenesis of Acute Kidney Injury.急性肾损伤的免疫发病机制
Toxicol Pathol. 2018 Dec;46(8):930-943. doi: 10.1177/0192623318799976. Epub 2018 Oct 3.
10
Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies.危重症儿童脓毒症急性肾损伤的组织病理学变化：一组尸检肾活检病例
Clin Exp Nephrol. 2017 Dec;21(6):1075-1082. doi: 10.1007/s10157-016-1343-z. Epub 2016 Oct 13.
引用本文的文献
1
Pancreatic β-cell regeneration in situ by the ALK3 agonist THR-123.ALK3激动剂THR-123介导的胰腺β细胞原位再生
Nat Commun. 2025 Jul 3;16(1):6121. doi: 10.1038/s41467-025-61534-2.
2
Inactivating the Innate Immune Receptor CD11b With a First-in-class Monoclonal Antibody Prolongs the Survival of Kidney Allografts in Nonhuman Primates.用一种首创的单克隆抗体使先天性免疫受体CD11b失活可延长非人灵长类动物肾移植的存活时间。
Transplantation. 2025 Aug 1;109(8):1350-1356. doi: 10.1097/TP.0000000000005370. Epub 2025 Mar 10.
3
Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension.血清肝细胞生长因子浓度与血压正常及未经治疗的动脉高血压个体的蛋白尿相关。
Biomedicines. 2024 Sep 30;12(10):2233. doi: 10.3390/biomedicines12102233.
4
Hydrogel-Mediated Local Delivery of Induced Nephron Progenitor Cell-Sourced Molecules as a Cell-Free Approach for Acute Kidney Injury.水凝胶介导的诱导肾祖细胞源分子的局部递送作为一种无细胞的急性肾损伤治疗方法。
Int J Mol Sci. 2024 Oct 2;25(19):10615. doi: 10.3390/ijms251910615.
5
Iron as an emerging therapeutic target in critically ill patients.铁作为危重症患者的一个新兴治疗靶点。
Crit Care. 2023 Dec 4;27(1):475. doi: 10.1186/s13054-023-04759-1.
6
Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference.儿科急性肾损伤病理生物学进展：第26届急性疾病质量改进倡议（ADQI）会议报告
Pediatr Nephrol. 2024 Mar;39(3):941-953. doi: 10.1007/s00467-023-06154-y. Epub 2023 Oct 4.
7
Mesenchymal stem cells therapy for acute kidney injury: A systematic review with meta-analysis based on rat model.间充质干细胞治疗急性肾损伤：基于大鼠模型的系统评价与Meta分析
Front Pharmacol. 2023 Apr 13;14:1099056. doi: 10.3389/fphar.2023.1099056. eCollection 2023.
8
Drugs in treating paediatric acute kidney injury.治疗小儿急性肾损伤的药物。
Pediatr Nephrol. 2023 Dec;38(12):3923-3936. doi: 10.1007/s00467-023-05956-4. Epub 2023 Apr 13.
9
Non-steroidal Anti-inflammatory Drugs: Clinical Implications, Renal Impairment Risks, and AKI.非甾体抗炎药：临床意义、肾功能损害风险与急性肾损伤
Adv Ther. 2023 May;40(5):2082-2096. doi: 10.1007/s12325-023-02481-6. Epub 2023 Mar 22.
10
Effect of water diuresis with hydrogen saturation on the course of acute kidney damage during the separation of oxidation and phosphorylation.水合-饱和氢对氧化磷酸化解偶联时急性肾损伤过程的影响。
J Med Life. 2022 Nov;15(11):1397-1402. doi: 10.25122/jml-2022-0155.
本文引用的文献
1
Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury.血红素加氧酶1作为急性肾损伤的治疗靶点
Am J Kidney Dis. 2017 Apr;69(4):531-545. doi: 10.1053/j.ajkd.2016.10.037. Epub 2017 Jan 27.
2
DNA damage response in nephrotoxic and ischemic kidney injury.肾毒性和缺血性肾损伤中的DNA损伤反应
Toxicol Appl Pharmacol. 2016 Dec 15;313:104-108. doi: 10.1016/j.taap.2016.10.022. Epub 2016 Oct 27.
3
Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults.危重症儿童和青年急性肾损伤的流行病学
N Engl J Med. 2017 Jan 5;376(1):11-20. doi: 10.1056/NEJMoa1611391. Epub 2016 Nov 18.
4
Signaling Crosstalk between Tubular Epithelial Cells and Interstitial Fibroblasts after Kidney Injury.肾损伤后肾小管上皮细胞与间质成纤维细胞之间的信号串扰
Kidney Dis (Basel). 2016 Oct;2(3):136-144. doi: 10.1159/000446336. Epub 2016 May 21.
5
N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.N-乙酰半胱氨酸联合去铁胺治疗长时间低血压患者并不能降低急性肾损伤的发生率：一项双盲、随机、安慰剂对照试验。
Crit Care. 2016 Oct 17;20(1):331. doi: 10.1186/s13054-016-1504-1.
6
Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence.基于间充质干细胞的肾脏疾病治疗：临床证据综述
Stem Cells Int. 2016;2016:4798639. doi: 10.1155/2016/4798639. Epub 2016 Sep 19.
7
Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases.骨形态发生蛋白-7在肾脏发育和疾病中的作用及调控
World J Stem Cells. 2016 Sep 26;8(9):288-96. doi: 10.4252/wjsc.v8.i9.288.
8
ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial.ABT-719用于预防高危心脏手术患者急性肾损伤：一项随机2b期临床试验
J Am Heart Assoc. 2016 Aug 20;5(8):e003549. doi: 10.1161/JAHA.116.003549.
9
Catalytic iron and acute kidney injury.催化铁与急性肾损伤
Am J Physiol Renal Physiol. 2016 Nov 1;311(5):F871-F876. doi: 10.1152/ajprenal.00388.2016. Epub 2016 Aug 17.
10
Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.左西孟旦超越心肌收缩力增强作用与急性心力衰竭：对心脏和其他器官多效性作用的证据：专家小组立场文件
Int J Cardiol. 2016 Nov 1;222:303-312. doi: 10.1016/j.ijcard.2016.07.202. Epub 2016 Jul 29.
Zotero 插件