Comprehensive, Real Time Monitoring of the Accumulation and Clearance of Small Molecules in Kidney Disease

全面、实时监测肾脏疾病中小分子的积累和清除

• 批准号: 10863011
• 负责人: Tod Edward Kippin
• 金额: $ 15万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-21 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10863011
• 关键词: Acceleration; Acute Renal Failure with Renal Papillary Necrosis; Animal Model; Animals; Biological Markers; Blood; Blood Glucose; Buffers; Cerebrospinal Fluid; Clinical; Continuous Glucose Monitor; Creatine; Creatinine; Detection; Development; Diagnosis; Dialysis procedure; Disease; Dose; Early Intervention; Effectiveness; End stage renal failure; Engineering; Ensure; Exhibits; Frequencies; Future; Goals; Health; Hour; In Situ; In Vitro; Injury to Kidney; Intercellular Fluid; Kidney; Kidney Diseases; Manuals; Measurement; Methods; Molecular; Monitor; Nature; Outcome; Patients; Performance; Plasma; Production; Provider; Renal Replacement Therapy; Renal clearance function; Renal function; Research; Resolution; Risk; Site; Solid; Speed; Stream; Techniques; Technology; Time; Tissues; Toxic effect; Toxin; Treatment Efficacy; Urea; Uremia; Validation; Work; aptamer; clinically relevant; improved; in vivo; individual patient; kidney dysfunction; minimally invasive; molecular marker; novel strategies; personalized medicine; pre-clinical; preclinical study; prevent; prototype; real time monitoring; response; sensor; small molecule; solute; subcutaneous; temporal measurement; tool; tool development; treatment optimization

: Current methods for monitoring kidney function and the effectiveness of renal replacement therapies, which rely on the ex-vivo measurement of plasma creatinine and urea, are inadequate on several fronts. Here, we propose to adapt electrochemical aptamer-based (EAB) sensors, the first platform molecular measurement technology shown to work in vivo, to enabling real-time, seconds-resolved monitoring of creatinine and urea in living subjects. To achieve this goal, we propose two specific aims. Our aim 1 goal is the validation of our existing, creatinine-detecting in-vivo EAB sensor for plasma measurements by comparison to ex-vivo analysis and to adapt it to the monitoring of creatinine in the subcutaneous space. Aim 2 will develop an in-vivo EAB sensor that supports multi-hour, drift-free, high temporal resolution measurements of plasma urea. The expected outcome of this work is the production of optimized EAB sensors against the two mostly clinically important biomarkers of renal function and renal replacement efficacy. Future development of these tools will set the stage to significantly improve our ability to study, detect, monitor, and treat all stages of kidney disease.

： 当前的监测肾功能和肾脏替代疗法的有效性，依赖于血浆肌酐和尿素的活体测量，在几个方面都不足。在这里，我们建议适应基于电化学适体的（EAB）传感器，这是显示在体内工作的第一个平台分子测量技术，以实现实时，几秒钟的分辨率监测肌酐和尿素的生物中的主体。为了实现这一目标，我们提出了两个具体目标。我们的目标1目标是通过与前体内分析进行比较，对现有的肌酐检测体内EAB传感器进行验证，以进行等离子体测量，并将其适应以监测皮下空间中肌酐的监测。 AIM 2将开发一个体内EAB传感器，该传感器支持血浆尿素的多小时，无漂移，高的时间分辨率测量。这项工作的预期结果是针对肾功能和肾脏替代功效的两个主要临床重要的生物标志物生产优化的EAB传感器。这些工具的未来开发将奠定阶段，以显着提高我们研究，检测，监测和治疗肾脏疾病的所有阶段的能力。