Imaging tools and models to study the effect of preterm birth on diabetic kidney disease
Jennifer Charlton   (Charlottesville, VA)
Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) in adults in the United States. There is an urgent unmet need to identify upstream risk factors that influence the risk and progression of diabetic kidney disease. This proposal will evaluate preterm birth as a significant risk factor in diabetic kidney disease progression. Preterm birth is common with ~10% of live births occurring before the 37th week of gestation. Those born preterm have an increased risk to develop CKD, likely due to early cessation of nephrogenesis and low nephron mass. Furthermore, studies have shown that preterm birth is a risk factor for the development of type 2 diabetes mellitus (T2DM) and females born early may be at greater risk for T2DM than preterm males. Neither clinical, nor preclinical studies, have investigated the influence of a preterm birth in the development or progression of diabetic kidney disease, representing a significant knowledge gap. Our group has developed tools to address this question and understand the molecular mechanisms that represent targetable therapeutics in this patient population. This proposal will create and investigate a diabetic mouse model born preterm using cutting-edge imaging and gene expression techniques. In Aim 1, we will characterize the structural phenotype of the kidney of a diabetic mouse model born preterm using cationic ferritin enhanced-MRI. We will use cationic ferritin enhanced-MRI to measure the glomerular number and spatially map size in diabetic mice born preterm. In Aim 2, we will compare the alterations of the kidney gene expression profiles in the diabetic preterm mouse to the diabetic term mouse. The Aims of this study align with the Diabetic Complications Consortium areas of emphasis both by advancing imaging techniques to measure nephron number as an early marker of diabetic kidney disease and examining sex differences in our model. At the conclusion of this work, we will have a fully phenotyped diabetic preterm mouse model to test therapeutic strategies for slowing progression in diabetic kidney disease.