Measuring metabolically active kidney tissue in autosomal dominant polycystic kidney disease

项目摘要/摘要： 常染色体显性遗传性多囊肾病(ADPKD)的特点是 在60岁之前，50%的患者需要肾脏替代治疗。动物模型 与肾脏缺氧有关，潜在原因是肾脏能量需求增加和 底物代谢受损，作为肾囊肿发生和发展的统一途径 一个潜在的治疗靶点。然而，ADPKD的一个主要临床研究障碍是准确和 无创测定患者肾组织耗氧量和代谢活性。 因此，需要能够区分和量化代谢活性和非活性的成像生物标记物 以增进我们对ADPKD代谢紊乱的了解，并告知 开发新的治疗靶点，而变化可能仍然是可逆的。 作为对NOT-DK-20-034的回应，调查小组试图开发一种体素智慧的药物动力学正电子 发射断层扫描(PET)模型，测量肾脏每个体素中11C-乙酸酯的清除量。 接下来，他们计划将11C-乙酸酯PET和多参数磁共振成像(MRI)相结合，以 确定代谢活跃的肾脏体积、肾血流量和囊性负荷之间的关系 ADPKD并保留肾功能的个体。为了实现这些目标，调查小组由以下人员组成 PET和MRI研究专家(Bjornstad、Gitmer、Kline、Blondin、Richard和Chin博士)以及ADPKD (Gitmer、Kline、Chonchol和Nowak博士)。目前的工作将有助于实现他们的长期目标 描述和定位ADPKD囊性生长的潜在机制。

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.