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

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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.