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

: 目前用于监测肾功能和肾替代疗法的有效性的方法依赖于血浆肌酐和尿素的离体测量，在几个方面是不够的。在这里，我们建议调整基于电化学适体（EAB）的传感器，这是第一个在体内工作的平台分子测量技术，以实现实时，秒级分辨的监测活体受试者的肌酐和尿素。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是通过与离体分析进行比较来验证我们现有的用于血浆测量的肌酐检测体内EAB传感器，并使其适用于监测皮下空间中的肌酐。目标2将开发一种体内EAB传感器，支持多小时、无漂移、高时间分辨率的血浆尿素测量。这项工作的预期成果是针对肾功能和肾脏替代疗效这两个临床上最重要的生物标志物生产优化的EAB传感器。这些工具的未来发展将为显着提高我们研究，检测，监测和治疗所有阶段肾脏疾病的能力奠定基础。

: 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.