Chronic kidney diseases (CKD) affect more than 10% of adult Americans, many of whom progress into end- stage renal failure. Glomerular fibrosis occurs in early stage of virtually all types of CKD, such as diabetic and hypertensive nephropathy. To better understand the initiation and progression of CKD, in this project we study the development of glomerular fibrosis, specifically the changes of renal tissue oxygenation and perfusion in the fibrotic development. As a major determinant for renal fibrosis and injury suggested by numerous studies, renal tissue hypoxia?s role in glomerular fibrosis has not been fully elucidated with rigorous in-vivo experiments. In this project with a well-controlled rat-fibrosis model, we will measure tissue oxygenation and perfusion using innovative and precise MRI techniques, and then accurately determine the fibrosis degree by kidney biopsy. Our preliminary study found significant decreases in MRI-measured perfusion and oxygenation in rats with intermediate glomerular fibrosis. In the proposed project, we will transfer our MRI protocol from current clinical MRI scanner to a dedicated 7T small-animal scanner to further improve measurement precision, and perform the MRI and biopsy measurements on rats with mild glomerular fibrosis (days 1 to 4 after fibrosis induction). Upon completion of this project, we will understand better the relationship between glomerular fibrosis and tissue oxygenation/perfusion, and thus gain insight into the initiation of CKD. With the knowledge gained in the current project, in future studies we will track the MRI-measured physiologic parameters for diabetic patients with microalbuminuria (high risk for diabetic nephropathy), and validate the parameters? capability in predicting diabetic nephropathy.

Public Health Relevance

Kidney fibrosis develops from the very beginning of chronic kidney disease (CKD), which affects 10% of adult Americans. In this project, we will assess physiologic changes induced by glomerular fibrosis in animal experiments. These experiments will help us better understand the initiation and progression of CKD, and would potentially improve CKD diagnosis and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK109349-01A1
Application #
9310730
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Rys-Sikora, Krystyna E
Project Start
2017-04-01
Project End
2021-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Utah
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112