Investigating the role of nephron mass in the progression of CKD using MRI

使用 MRI 研究肾单位质量在 CKD 进展中的作用

• 批准号: 10472810
• 负责人: Kevin M Bennett
• 金额: $ 10万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10472810
• 关键词: Acute; Adult; Age; Animals; Biological Markers; Birth; Blood Pressure; Cations; Cells; Childhood; Chronic Kidney Failure; Development; Environment; Exposure to; Ferritin; Focal Segmental Glomerulosclerosis; Foundations; Funding; Glomerular Filtration Rate; Goals; Histology; Human; Hypertension; Hypertrophy; Individual; Investigation; Kidney; Lead; Low Birth Weight Infant; Magnetic Resonance Imaging; Maps; Measures; Modeling; Morphology; Nephrons; Papio; Pathology; Pathway interactions; Perinatal; Phenotype; Predisposition; Pregnancy; Premature Birth; Proteins; Rattus; Risk; Role; Systemic hypertension; Work; clinically relevant; glomerulosclerosis; high risk; in vivo; neonate; offspring; tool

The long-term goal of our work is to understand the mechanisms that lead from a low nephron mass to susceptibility to hypertension (HTN) and chronic kidney diseases (CKD), to facilitate therapies to slow or halt progression of CKD. Low birth weight infants (<2.5 kg) are born with fewer nephrons and have up to a four-fold greater risk to develop HTN and CKD, often detectable in childhood. The proposed pathway leading from a low nephron mass to CKD is systemic HTN, compensatory hypertrophy of remaining glomeruli, and glomerulosclerosis. However, this pathway has not been investigated in vivo, and the threshold of functional nephron mass that precipitates CKD is unknown. Here, we will apply cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) to phenotype long-term CKD in two clinically relevant rat models of low nephron mass at birth that develop CKD: 1) Offspring exposed to maternal protein restriction and 2) Offspring born preterm. We will fully characterize the kidney phenotype and pathology at the age of 24 weeks in both models. This work will set the stage for a longitudinal in vivo investigation of CKD in these animals.

我们工作的长期目标是了解肾单位质量低导致高血压 (HTN) 和慢性肾脏病 (CKD) 易感性的机制，以促进减缓或阻止 CKD 进展的治疗。低出生体重婴儿（<2.5 公斤）出生时肾单位较少，患高血压和慢性肾病的风险高达四倍，这些风险通常在儿童时期就被发现。所提出的从低肾单位质量导致 CKD 的途径是全身性 HTN、剩余肾小球的代偿性肥大和肾小球硬化。然而，该途径尚未在体内进行研究，并且引发 CKD 的功能性肾单位质量阈值尚不清楚。在这里，我们将应用阳离子铁蛋白增强磁共振成像 (CFE-MRI) 对两种出生时肾单位质量较低、发展为 CKD 的临床相关大鼠模型中的长期 CKD 进行表型分析：1) 后代受到母体蛋白质限制，2)后代早产。我们将在 24 周龄时全面描述两种模型的肾脏表型和病理学特征。这项工作将为这些动物体内慢性肾病的纵向研究奠定基础。