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从低肾元质量导致高血压（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，发生HTN和CKD的风险高达4倍，通常在儿童时期就可以检测到。从低肾元质量到CKD的可能途径是全身性HTN、剩余肾小球代偿性肥大和肾小球硬化。然而，这一途径尚未在体内进行研究，并且导致CKD的功能性肾单位质量的阈值尚不清楚。在这里，我们将应用阳离子铁蛋白增强磁共振成像（CFE-MRI）对两种临床相关的大鼠模型进行长期CKD的表型分析：1)暴露于母体蛋白质限制的后代和2)早产的后代。我们将在两种模型中充分表征24周龄时肾脏表型和病理。这项工作将为CKD在这些动物体内的纵向研究奠定基础。

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.