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

： 目前监测肾功能和肾脏替代疗法有效性的方法依赖于体外测量血浆肌酐和尿素，在几个方面存在不足。在这里，我们建议采用基于电化学适配子(EAB)的传感器，这是第一个被证明在体内工作的平台分子测量技术，以实现对活体受试者肌酐和尿素的实时、秒分辨监测。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是通过与体外分析的比较，验证我们现有的、可检测肌酐的在体EAB传感器用于血浆测量，并使其适用于皮下空间的肌酐监测。AIM 2将开发一种体内EAB传感器，支持数小时、无漂移、高时间分辨率的血浆尿素测量。这项工作的预期结果是针对肾功能和肾脏替代疗效这两个最具临床重要性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著提高我们研究、检测、监测和治疗肾脏疾病所有阶段的能力奠定基础。

: 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.