Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
基本信息
- 批准号:10670112
- 负责人:
- 金额:$ 73.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:Academic Medical CentersAcuteAcute Renal Failure with Renal Papillary NecrosisAdultAffinityAnimal ModelAnimalsAtrial FibrillationAttenuatedBindingBloodBostonCD14 geneCardiacCardiac Surgery proceduresCardiac VolumeCardiopulmonary BypassCell surfaceCessation of lifeChronicChronic Kidney FailureCirculationClinicalComplexComplicationConduct Clinical TrialsControlled EnvironmentCreatinineCritical IllnessDataDeferoxamineDeliriumDevelopmentDouble-Blind MethodEnrollmentExcretory functionExposure toFecesFerritinFlow CytometryFunctional disorderHemeHemoglobinHemolysisHospitalsHourHumanHypotensionIncidenceInflammationInflammatoryInfrastructureInfusion proceduresInjuryInjury to KidneyInterleukin-6Intravenous infusion proceduresInvestigationIronIron Chelating AgentsIron ChelationIron OverloadIsoprostanesKidneyLCN2 geneLeft Ventricular Ejection FractionMeasuresMechanical ventilationMediatingMyocardial InfarctionNormal salineOperative Surgical ProceduresOrganOutcomeOutputOxidative StressPathogenesisPatientsPeroxidasesPhasePhenotypePhysiologicalPlacebosPlasmaPlayPostoperative PeriodPre-Clinical ModelPreventionProductionProspective, cohort studyPublic HealthRandomizedRandomized, Controlled TrialsRenal Replacement TherapyRiskRoleSepsisSerumSeveritiesSurgeonTNF geneTestingTherapeuticTranscriptTransferrinTubular formationUrinecytokineexperiencehigh riskimprovedinflammatory markerinjury preventioninnovationinsightiron metabolismmonocytemortality riskmyocardial injurynephrotoxicitynew therapeutic targetnext generationnovelorgan injuryoxidative damageparticipant enrollmentperipheral bloodpharmacologicprecision medicinepreventprimary endpointprophylacticresearch studysecondary endpointtranscriptometranscriptome sequencingtranslational studyurinary
项目摘要
PROJECT SUMMARY
Acute kidney injury (AKI) is a common and often devastating complication of cardiac surgery, critical
illness, and other clinical settings. No pharmacologic therapy reliably prevents or treats AKI. Abundant data
from both animal models and humans indicates that iron plays a key role in the pathogenesis of AKI,
particularly in the setting of cardiac surgery. We propose a phase II, double-blind, randomized controlled trial
to test whether administration of the iron chelating agent, deferoxamine (DFO), prevents AKI following cardiac
surgery. We will enroll 300 adult patients at high risk of AKI following cardiac surgery at three major academic
medical centers in Boston. Patients will be randomly assigned, in a 1:1 fashion (n=150/group), to receive DFO
(30 mg/kg) or an equal volume of normal saline. DFO (or normal saline) will be administered as a continuous
24-hour intravenous infusion beginning immediately prior to surgery.
In Aim 1 we will test the effects of DFO compared to placebo on the incidence of postoperative AKI
(primary endpoint). AKI will be defined by changes in serum creatinine and urine output, according to the
KDIGO criteria. As secondary endpoints, we will assess longitudinal changes in urinary tubular injury markers,
NGAL and KIM-1. We will also test the effects of DFO on the incidence of the following common and
biologically plausible extrarenal postoperative endpoints: myocardial infarction, atrial fibrillation, delirium,
prolonged mechanical ventilation, and sepsis.
In Aim 2 we will tests the effects of DFO compared to placebo on longitudinal measures of circulating
iron and oxidative stress, and the inflammatory phenotype of monocytes. Serum iron parameters will include
catalytic iron – a toxic, non-physiologic iron species – as well as transferrin saturation and ferritin. Plasma
markers of oxidative stress will include F(2)-isoprostane and myeloperoxidase. We will also assess the effect
of DFO versus placebo on monocyte (CD14+) expression of IL-6, TNFα, and other markers of inflammation
using flow cytometry. In exploratory analyses, we will use next-generation RNA sequencing (RNA-Seq) to
assess the effect of DFO on the transcriptome of monocytes, which will facilitate discovery of novel transcripts
influenced by DFO. We will also determine the extent to which the effect of DFO on renal and extrarenal acute
organ injury (assessed in Aim 1) varies depending on the preoperative expression of key parameters
measured in Aim 2.
In aggregate, the studies proposed here will test a novel and promising therapeutic strategy for AKI
prevention. These studies have strong potential to improve clinical outcomes in patients at risk for AKI.
Further, the translational studies proposed here will yield important scientific insights into the role of iron
metabolism in the pathophysiology of AKI.
项目总结
项目成果
期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.
癌症患者的肌肉减少症、肥胖以及胱抑素 C 和基于肌酐的估计肾小球滤过率之间的巨大不一致。
- DOI:10.1002/jcsm.13469
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Hanna,PaulE;Ouyang,Tianqi;Tahir,Ismail;Katz-Agranov,Nurit;Wang,Qiyu;Mantz,Lea;Strohbehn,Ian;Moreno,Daiana;Harden,Destiny;Dinulos,JamesE;Cosar,Duru;Seethapathy,Harish;Gainor,JustinF;Shah,SachinJ;Gupta,Shruti;Leaf,DavidE;
- 通讯作者:
Platelet Factor 4 Antibodies and Severe AKI.
- DOI:10.34067/kid.0000000000000287
- 发表时间:2023-12-01
- 期刊:
- 影响因子:0
- 作者:Thomas C;Ali R;Park I;Kim H;Short S;Kaunfer S;Durai L;Yilmam OA;Shenoy T;Battinelli EM;Al-Samkari H;Leaf DE
- 通讯作者:Leaf DE
Intraoperative Oxygen Practices in Cardiac Surgery: A National Survey.
- DOI:10.1053/j.jvca.2022.01.019
- 发表时间:2022-08
- 期刊:
- 影响因子:2.8
- 作者:
- 通讯作者:
Tocilizumab in COVID-19: some clarity amid controversy.
- DOI:10.1016/s0140-6736(21)00712-1
- 发表时间:2021-05-01
- 期刊:
- 影响因子:0
- 作者:Gupta S;Leaf DE
- 通讯作者:Leaf DE
Histopathologic Correlates of Kidney Function: Insights From Nephrectomy Specimens.
肾功能的组织病理学相关性:来自肾切除标本的见解。
- DOI:10.1053/j.ajkd.2020.08.015
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Li,Ping;Gupta,Shruti;Mothi,SurajS;Rennke,HelmutG;Leaf,DavidE;Waikar,SushrutS;McMahon,GearoidM
- 通讯作者:McMahon,GearoidM
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David Evan Leaf其他文献
David Evan Leaf的其他文献
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{{ truncateString('David Evan Leaf', 18)}}的其他基金
Hepcidin-Ferroportin-Iron Axis in Cardiac Surgery-associated Acute Kidney Injury
心脏手术相关急性肾损伤中的铁调素-铁转运蛋白-铁轴
- 批准号:
10659183 - 财政年份:2022
- 资助金额:
$ 73.48万 - 项目类别:
Hepcidin-Ferroportin-Iron Axis in Cardiac Surgery-associated Acute Kidney Injury
心脏手术相关急性肾损伤中的铁调素-铁转运蛋白-铁轴
- 批准号:
10444522 - 财政年份:2022
- 资助金额:
$ 73.48万 - 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
- 批准号:
10442625 - 财政年份:2020
- 资助金额:
$ 73.48万 - 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
- 批准号:
10249293 - 财政年份:2020
- 资助金额:
$ 73.48万 - 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
- 批准号:
10034169 - 财政年份:2020
- 资助金额:
$ 73.48万 - 项目类别:
Precision Medicine Approach to Vitamin D3 Administration in Critical Illness
危重疾病维生素 D3 给药的精准医学方法
- 批准号:
10444999 - 财政年份:2019
- 资助金额:
$ 73.48万 - 项目类别:
Precision Medicine Approach to Vitamin D3 Administration in Critical Illness
危重疾病维生素 D3 给药的精准医学方法
- 批准号:
9916797 - 财政年份:2019
- 资助金额:
$ 73.48万 - 项目类别:
Precision Medicine Approach to Vitamin D3 Administration in Critical Illness
危重疾病维生素 D3 给药的精准医学方法
- 批准号:
10217234 - 财政年份:2019
- 资助金额:
$ 73.48万 - 项目类别:
Dysregulated Mineral Metabolism in Acute Kidney Injury
急性肾损伤时矿物质代谢失调
- 批准号:
8702918 - 财政年份:2013
- 资助金额:
$ 73.48万 - 项目类别:
Dysregulated Mineral Metabolism in Acute Kidney Injury
急性肾损伤时矿物质代谢失调
- 批准号:
8588596 - 财政年份:2013
- 资助金额:
$ 73.48万 - 项目类别:
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