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

我们工作的长期目标是了解低肾单位质量导致高血压（HTN）和慢性肾脏疾病（CKD）易感性的机制，以促进减缓或停止CKD进展的治疗。低出生体重婴儿（<2.5 kg）出生时肾单位较少，患HTN和CKD的风险高出4倍，通常在儿童时期即可检测到。从低肾单位质量到CKD的拟议途径是系统性HTN、剩余肾小球的代偿性肥大和肾小球硬化。然而，这一途径尚未在体内研究，功能性肾单位质量沉淀CKD的阈值是未知的。在这里，我们将应用阳离子铁蛋白增强磁共振成像（CFE-MRI）在两个临床相关的大鼠模型中的表型长期CKD的低肾单位质量在出生时发展CKD：1）后代暴露于母体蛋白质限制和2）后代早产。我们将在两种模型中充分表征24周龄时的肾脏表型和病理学。这项工作将为这些动物中CKD的纵向体内研究奠定基础。

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.