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Renal Oxygenation and Mitochondrial Function in AKI

AKI 中的肾氧合和线粒体功能

基本信息

批准号：
9906221
负责人：
Prabhleen Singh
金额：
$ 34.88万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-18 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9906221
关键词：
5&apos -AMP-activated protein kinase ATP Synthesis Pathway Acute Renal Failure with Renal Papillary Necrosis Address Animals Apoptosis Architecture Area Autophagocytosis Bioenergetics Biogenesis Cells Chimeric Proteins Clinical Critical Illness Data Development Electron Microscopy Embryo Fibroblasts Generations Genetic Goals Hour Hypoxia Impairment Injury Injury to Kidney Investigation Kidney Kidney Diseases Lead Medical Metabolism Methods Micropuncture Mitochondria Modeling Molecular Morbidity - disease rate Morphology Mus Natural regeneration Nephrons Outcome Oxygen Oxygen Consumption Pathogenesis Pathway interactions Patients Peptides Pharmacology Phenotype Physiological Play Predisposition Production Proteins Quality Control Reactive Oxygen Species Renal Blood Flow Renal Tissue Renal function Research Role Secondary to Sepsis Skeletal Muscle Sodium Stress Study models Techniques Therapeutic Translating Treatment Efficacy Tubular formation cecal ligation puncture cell injury clinically relevant cost hemodynamics improved in vivo inhibitor/antagonist insight mitochondrial dysfunction mitochondrial metabolism mortality nephrotoxicity new therapeutic target novel outcome forecast regional difference response sensor septic

项目摘要

PROJECT SUMMARY Acute kidney injury (AKI) in the setting of sepsis is frequently observed and is a significant clinical problem with high levels of morbidity and mortality. One of the major barriers to the progress in the field is the lack of understanding of the pathogenesis of AKI in this setting. The specific aims of this proposal is to investigate the primary and/or secondary changes in mitochondrial function and morphology in sepsis associated AKI that lead to inefficient oxygen utilization by the kidney. The proposal also aims to determine the effects of mitochondrial dysfunction and elevated oxygen utilization in the kidney on overall renal function and kidney injury in the setting of sepsis. The research strategy is to employ a comprehensive investigative approach for an integrative understanding of pathogenesis of sepsis associated AKI, using the clinically relevant cecal ligation and puncture model of sepsis. The methods will include physiological techniques such as whole animal kidney clearance, renal blood flow and micropuncture and molecular techniques to assess mitochondrial bioenergetics, ATP, reactive oxygen species generation and electron microscopy to assess mitochondrial morphology and dynamics. These investigations will provide important insights into hemodynamic and non-hemodynamic factors in the pathogenesis of sepsis-associated AKI and identify specific mechanistic pathways and novel therapeutic targets. The insights obtained will be will be valuable beyond the model studied given the wide-spread implications of mitochondrial dysfunction in kidney disease.

项目总结