Noninvasive MRI techniques to detect pathology in murine models of renal disease

无创 MRI 技术检测小鼠肾病模型的病理学

• 批准号: 9769015
• 负责人: Kevin M Bennett
• 金额: $ 20.51万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769015
• 关键词: Acute Kidney Tubular Necrosis; Acute Renal Failure with Renal Papillary Necrosis; Address; Adult; American; Animal Model; Atlases; Biological Markers; Biomedical Engineering; Birth; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cations; Chronic Kidney Failure; Clinical; Clinical Trials; Complement; Data; Development; Diagnostic; Disease; Disease Progression; End stage renal failure; Essential Hypertension; Evaluation; Event; Exposure to; Ferritin; Fibrosis; Folic Acid; Foundations; Future; Glomerular Filtration Rate; Goals; Heterogeneity; Histologic; Histology; Human; Hypertrophy; Imaging Techniques; Individual; Injury to Kidney; Investigation; Kidney; Kidney Diseases; Longevity; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Maps; Masks; Measurement; Measures; Methods; Modeling; Morphology; Mus; Nephrons; Organ; Pathology; Patients; Phase; Physicians; Predictive Value; Proteinuria; Ramipril; Renal function; Risk; Safety; Scientist; Severities; Structure; Symptoms; Techniques; Therapeutic; Therapeutic Intervention; Time; Transforming Growth Factor beta; Translations; Tubular formation; Vasodilation; Work; anatomic imaging; base; clinically relevant; contrast enhanced; diagnostic biomarker; drug development; early detection biomarkers; glomerulosclerosis; imaging biomarker; in vivo; kidney allograft; malignant breast neoplasm; mouse model; multidisciplinary; new technology; novel; novel therapeutics; overexpression; predictive marker; renal damage; response; tool

Project Summary/Abstract The broad, long-term goal of this multi-disciplinary collaborative of biomedical engineers and physician- scientists is to develop early, non-invasive methods to identify individuals at risk of developing chronic kidney disease (CKD). Current methods to detect kidney disease are only useful when more than half of the filtering units of the kidney, nephrons, are nonfunctional. Nephron number is determined at birth, declines over the lifespan of a human and is directly related to the development of chronic kidney and cardiovascular disease. Unfortunately, there are no techniques to count the total number of functioning nephrons in living individuals. Additionally, there is no way to integrate the major compartments of the kidney, such as glomerular changes to those in the vasculature or tubulointerstitial space. A diagnostic biomarker to assess renal microstructure, such as number and volume of glomeruli, could significantly benefit patients: earlier therapeutic intervention, novel endpoints for assessing renal safety in clinical trials for drug development, and for renal allografts allocation. This work has three Specific Aims: 1) We will assess the changes in the glomeruli by MRI during the development of CKD using two mouse models: a congenital reduction in nephron number and a glomerulosclerosis model of CKD. We will compare the changes in glomerular microstructure to the vascular and tubular compartments and to traditional biomarkers of renal disease. 2) We will determine the time course of tubulointerstitial pathology using MRI in mouse model representing the transition from acute kidney injury to chronic kidney disease. 3) We will determine the effect of ACE inhibition of the microstructure of the kidney in a mouse model of essential hypertension. At the conclusion of this project, we will have the first comprehensive, integrated MRI-based evaluation of the kidney, powerful data to inform the translation of these MRI-based biomarkers for future studies to predict kidney disease progression.

项目总结/摘要 生物医学工程师和医生的多学科合作的广泛、长期目标- 科学家们正在开发早期的、非侵入性的方法来识别有患慢性肾病风险的个体。 病（CKD）。目前检测肾脏疾病的方法只有在超过一半的过滤 肾脏的单位肾单位没有功能。肾单位数量在出生时确定，随着年龄的增长而下降。 它影响人类的寿命，并与慢性肾脏和心血管疾病的发展直接相关。 不幸的是，目前还没有技术来计算活体中有功能的肾单位的总数。 此外，没有办法整合肾脏的主要隔室，如肾小球变化， 那些在脉管系统或肾小管间质空间中的。用于评估肾脏微观结构的诊断生物标志物，例如 如肾小球的数量和体积，可以显着受益患者：早期治疗干预，新的 药物开发临床试验中评估肾脏安全性的终点，以及肾脏移植物分配。 本工作有三个具体的目的：1）我们将通过MRI评估肾小球的变化， 使用两种小鼠模型研究CKD的发展：先天性肾单位数量减少和 CKD的肾小球硬化模型。我们将比较肾小球微结构和血管微结构的变化， 和管状室以及传统的肾病生物标志物。2)我们将确定时间进程 在小鼠模型中使用MRI观察肾小管间质病理学， 慢性肾脏疾病。3)我们将确定ACE抑制对肾脏微结构的影响， 小鼠原发性高血压模型。在这个项目结束时，我们将有第一个全面的， 基于MRI的肾脏综合评价，为这些基于MRI的 用于未来研究的生物标志物，以预测肾脏疾病进展。

项目成果

New imaging tools to measure nephron number in vivo: opportunities for developmental nephrology.

• DOI: 10.1017/s204017442000001x
• 发表时间: 2021-04
• 期刊: Journal of developmental origins of health and disease
• 影响因子: 1.7
• 作者: Bennett KM;Baldelomar EJ;Morozov D;Chevalier RL;Charlton JR
• 通讯作者: Charlton JR

Delayed Umbilical Cord Clamping is Not Associated with Acute Kidney Injury in Very Low Birth Weight Neonates.

延迟脐带结扎与极低出生体重新生儿的急性肾损伤无关。

• DOI: 10.1055/s-0039-1697671
• 发表时间: 2020
• 期刊: American journal of perinatology
• 影响因子: 2
• 作者: Harer,MatthewW;McAdams,RyanM;Conaway,Mark;Vergales,BrookeD;Hyatt,DylanM;Charlton,JenniferR
• 通讯作者: Charlton,JenniferR

Nephron number and its determinants: a 2020 update.

• DOI: 10.1007/s00467-020-04534-2
• 发表时间: 2021-04
• 期刊: Pediatric nephrology (Berlin, Germany)
• 作者: Charlton JR;Baldelomar EJ;Hyatt DM;Bennett KM
• 通讯作者: Bennett KM