Measuring metabolically active kidney tissue in autosomal dominant polycystic kidney disease

测量常染色体显性多囊肾病中代谢活跃的肾组织

• 批准号: 10281837
• 负责人: Petter M Bjornstad
• 金额: $ 24.21万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10281837
• 关键词: 3-Dimensional; Acetates; Address; Adenosine Triphosphate; Adult; Affect; Age; Animal Model; Automobile Driving; Autosomal Dominant Polycystic Kidney; Calcium; Cell Respiration; Chlorides; Citric Acid Cycle; Classification; Clinical Research; Consumption; Cyst; Cystic kidney; Data; Development; Disease; Drug Kinetics; End stage renal failure; Enrollment; Exhibits; Experimental Models; Fasting; Financial compensation; Glomerular Filtration Rate; Goals; Growth; Growth and Development function; Heart; Height; Hypoxia; Hypoxia Inducible Factor; Impairment; Individual; Kidney; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Mitochondria; Modeling; Motion; Na(+)-K(+)-Exchanging ATPase; Oxidative Stress; Oxygen; Oxygen Consumption; PKD1 gene; PKD2 gene; Participant; Pathway interactions; Patients; Phase; Play; Positron-Emission Tomography; Production; Renal Blood Flow; Renal Replacement Therapy; Renal function; Research; Role; Structure; System; T2 weighted imaging; Techniques; Therapeutic; Tissues; Woman; Work; imaging biomarker; imaging modality; imaging program; improved; kidney preservation; mitochondrial dysfunction; multimodality; new therapeutic target; novel; renal hypoxia; response; stem; therapeutic target

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.

项目摘要/摘要： 常染色体显性多囊肾病 (ADPKD) 的特征是 50% 的 60 岁患者患有多发性囊肿，需要肾脏替代治疗。动物模型 涉及肾脏缺氧，可能源于肾脏能量需求增加和肾脏能量需求增加之间的不匹配 底物代谢受损，作为肾囊肿发生和进展的统一途径 一个潜在的治疗靶点。然而，ADPKD 临床研究的一个主要障碍是如何准确、准确地诊断 ADPKD。 无创地确定受影响患者肾组织的耗氧量和代谢活动。 因此，需要能够区分和量化代谢活跃与非活跃的成像生物标志物 肾组织以增进我们对 ADPKD 代谢扰动的理解并为 开发新的治疗靶点，而变化可能仍然是可逆的。 为了响应 NOT-DK-20-034，研究团队寻求开发一种体素药代动力学正电子 发射断层扫描 (PET) 模型，测量肾脏每个体素中 11C-乙酸盐的清除率。 接下来，他们计划将 11C-醋酸盐 PET 和多参数磁共振成像 (MRI) 结合起来， 确定代谢活跃的肾体积、肾血流量和囊肿负荷之间的关系 患有 ADPKD 且肾功能保留的个体。为了实现这些目标，调查小组包括 PET 和 MRI 研究专家（Bjornstad、Gitomer、Kline、Blondin、Richard 和 Chin 博士）以及 ADPKD （Gitomer、Kline、Chonchol 和 Nowak 博士）。目前的工作将有助于他们的长期目标 表征并针对 ADPKD 囊肿生长的潜在机制。

项目成果

Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

常染色体显性多囊肾病的肾脏能量学和囊肿负担：一项试点研究。

• 发表时间: 2024-04-13
• 作者: Bjornstad, Petter;Richard, Gabriel;Choi, Ye Ji;Nowak, Kristen L;Steele, Cortney;Chonchol, Michel B;Nadeau, Kristen J;Vigers, Timothy;Pyle, Laura;Tommerdahl, Kalie;van Raalte, Daniel H;Hilkin, Allison;Driscoll, Lynette;Birznieks, Carissa;Hopp
• 通讯作者: Hopp