Measuring metabolically active kidney tissue in autosomal dominant polycystic kidney disease

项目摘要/摘要：

PROJECT SUMMARY / ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by development and growth of multiple cysts requiring kidney replacement therapy in 50% of patients by the age of 60 years. Animal models implicate kidney hypoxia, potentially stemming from a mismatch between increased renal energy demand and impaired substrate metabolism, as a unifying pathway in the development and progression of kidney cysts and a potential therapeutic target. Yet, a major clinical research impediment in ADPKD is a way to accurately and non-invasively determine oxygen consumption and metabolic activity of kidney tissue in affected patients. Thus, there is a need for imaging biomarkers that can differentiate and quantify metabolically active vs. inactive kidney tissue to advance our understanding of the metabolic perturbations of ADPKD and inform the development of new therapeutic targets while changes may still be reversible. In response to NOT-DK-20-034, the investigative team seeks to develop a voxel-wise pharmacokinetic positron emission tomography (PET) model that measures the clearance of 11C-acetate in every voxel of the kidney. Next, they plan to integrate 11C-acetate PET and multiparametric magnetic resonance imaging (MRI) to determine the relationships among metabolically active kidney volume, renal blood flow and cyst burden in individuals with ADPKD and preserved kidney function. To achieve these goals, the investigative team consists of experts in PET and MRI research (Drs. Bjornstad, Gitomer, Kline, Blondin, Richard and Chin), and ADPKD (Drs. Gitomer, Kline, Chonchol, and Nowak). The current work will contribute to their long-term goal to characterize and target the mechanisms underlying cyst growth in ADPKD.