Adenosine 2A Receptor Agonist in Diabetic Nephropathy

腺苷 2A 受体激动剂治疗糖尿病肾病

• 批准号: 7895818
• 负责人: KAMBIZ KALANTARI
• 金额: $ 13.08万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895818
• 关键词: ATL 146e; Acids; Acute; Address; Adenosine; Age; Agonist; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Award; Blood flow; Bone Marrow; CCL2 gene; Cardiology; Cells; Chronic; Clinical Research; Clinical Trials; Complex; Complications of Diabetes Mellitus; Control Groups; Creatinine; Crossover Design; Deposition; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Disease Progression; Dose; Enalaprilat; End stage renal failure; Endotoxins; Environment; Evaluation; Excretory function; Exposure to; Filtration; Foundations; Funding; Future; Gender; Glomerular Filtration Rate; Growth Factor; Hand; Health; Health Sciences; Human; Incidence; Individual; Inflammation; Inflammatory; Infusion procedures; Injury; Interleukin-1 alpha; Interleukin-10; Interleukin-6; Intervention Studies; Intravenous; Iothalamate; Kidney; Kidney Diseases; Lead; Master' s Degree; Measures; Mentors; Methods; Microbubbles; Modeling; Monitor; Morbidity - disease rate; Names; Nephrology; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Pilot Projects; Plasma; Play; Population Study; Property; Proteins; Proteinuria; Public Health; Purinergic P1 Receptors; RANTES; Race; Randomized; Reducing Agents; Renal Blood Flow; Renin-Angiotensin System; Reperfusion Injury; Reporting; Research; Research Personnel; Resources; Role; Safety; Science; Serum; Stretching; Techniques; Testing; Therapeutic; Tissues; Training; Translating; Ultrasonography; United States National Institutes of Health; Universities; Urine; Virginia; age group; arteriole; base; career; cytokine; design; diabetic; diabetic patient; glomerulosclerosis; healthy volunteer; hemodynamics; human subject; industry partner; inflammatory marker; macrophage; mesangial cell; mortality; novel; patient oriented; preclinical study; prevent; programs; receptor; response; standard of care; urinary

DESCRIPTION (provided by applicant): Activation of inflammatory pathways within the kidney tissue is one of the pathogenic mechanisms in the development of diabetic nephropathy. Activation of adenosine A2A receptors (A2ARs) reduces inflammation. In animal models of acute renal injury, administration of ATL146e, a selective A2AR agonist, reduces inflammation and protects tissue. A2A agonists also reduce inflammation and proteinuria and prevented histological changes in an animal model of diabetic nephropathy. Currently, this compound is being used in phase I human studies. We hypothesized that ATL146e given to proteinuric diabetic subjects will reduce inflammation. Our specific aims are to compare the effects of intravenous ATL146e and ACE inhibitor, enalprilat, on, 1. urinary concentration of inflammatory cytokines and growth factors, 2. total, cortical and medullary renal blood flows and GFR and 3. Proteinuria. A pilot study will be done to determine the optimum duration of ATL146e infusion. Novel technique of contrast enhanced ultrasound (CEU) as well clearance techniques will be used to monitor renal hemodynamic changes. CEU has been used extensively in the field of cardiology and recent studies have demonstrated applications for its use in nephrology as well. Tha candidate is currently conducting GCRC-sponsored study using CEU in monitoring changes in regional renal blood flow in healthy human subjects. This project combines the strengths of the University of Virginia as a leader in both the study of adenosine A2A receptor agonist and diabetes. Dr Mark Okusa, candidate's promary mentor, has 7 years of background in research on A2A agonist. Dr. Eugene Barrett, the co-mentor, is an internationally recognized name in the field of diabetes research and the Director of the NIH- sponsored GCRC at UVA. This K23 leverages the strength of the insitutional commitment toward deveveloping indendent careers in clinical investigation, the research environment in diabetic kidney disease and adenosine receptors, and the resources of the General Clinical Research Center at the Unvirsity of Virginia. Funding will permit the applicant to receive formal training and a masters degree in Health Evaluation Sciences, Clinical Investigation and Patient Orients Researcg track. Dr William Knaus, the director of the Department of Public Health Sciences at UVA, is an advisor to the candidate and has designed a specific plan for the candidate's training and will monitor his progress during the years of award support.

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