Nanoengineering Renal Replacement Therapy

纳米工程肾脏替代疗法

• 批准号: 10690367
• 负责人: Saeed Moghaddam
• 金额: $ 10万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10690367
• 关键词: Address; Blood; Blood Pressure; Blood Vessels; Blood flow; Cessation of life; Clinical; Devices; Diabetes Mellitus; Dialysis patients; Dialysis procedure; Drops; End stage renal failure; Ensure; Excision; Fiber; Fright; Goals; Government; Growth; Health; Heart; Hemodialysis; Hemorrhage; Home; Hour; Human body; Hypertension; Kidney; Liquid substance; Measurement; Measures; Medicare; Membrane; Metabolic; Methods; Microfluidics; Miniaturization; Modeling; Nurses; Outcome; Oxides; Patient Care; Patients; Performance; Permeability; Persons; Procedures; Process; Pump; Quality of life; Renal Replacement Therapy; Renal function; Reporting; Research; Resistance; Risk; Risk Factors; Safety; Shoulder; Side; Stream; System; Technology; Testing; Transmembrane Transport; Treatment outcome; base; blood filter; blood pressure regulation; cost; design; dosage; graphene; hemocompatibility; hemodynamics; iterative design; meter; nanoengineering; nanomembrane; operation; patient safety; pressure; research and development; standard care; theories; wasting

End stage renal disease (ESRD) is currently responsible for ~50,000 deaths annually in the US. The number of patients with ESRD is progressively increasing, with diabetes and high blood pressure being the two leading causes. The standard care for these patients is lifelong hemodialysis (HD) treatment thrice weekly, but dialysis poorly mimics the natural kidney function. Filtering the blood for only 12 hours per week with dialysis is both non-physiological and inadequate. More frequent dialysis is preferred, as it allows steady waste and fluid removal resulting in superior metabolic and hemodynamic control. As patients are shifted from the typical thrice-weekly regime to one of daily in-home dialysis, significant improvements in the clinical outcome and the quality of life are reported. However, the implementation of daily dialysis on a large scale is difficult. Some of these are the inability or unwillingness of patients to dialyze at home, the lack of staffing both in nurses and technicians to provide more treatments in the dialysis units, and the reluctance of governmental payers to shoulder the expense of more frequent dialysis. In 2018, the Medicare spending alone on CKD and ESRD patients was about $120 billion. To address this great health and societal challenge, miniaturization of components and systems and reducing complexity while ensuring safety are at the heart of dialysis research and development efforts. One of the key barriers is the limitations of the current membrane technology. The current membrane module is bulky, needing an extracorporeal blood circuit consisting of meters of tubing, a pump, and other auxiliary components. Establishing the blood circuit for each dialysis session must be done by a qualified person and presents a major risk factor hampering efforts on expanding in-home frequent dialysis and patient’s independence. To address patients’ safety concerns (through reducing/eliminating the risk of bleeding), enhance affordability in the US and throughout the world and enable new vascular access options, under a recent R21 project, we have nanoengineered a new membrane that is 40x more permeable than the high-flux commercial membranes. This new membrane has demonstrated excellent sieving performance, enabling breakthrough reduction of the dialyzer size by two orders of magnitude such that it can be directly connected to the vascular access eliminating the extracorporeal blood circuit and pump (the dialyzer can be operated using just arterial blood pressure) alleviating the fear of exsanguination that is impeding the growth of in-home dialysis. The overarching objective of the proposed research is to evaluate the hydrodynamic performance of a new microfluidic dialyzer model for incorporation of the new high throughput nanomembrane and evaluate differences in flow regime relative to conventional hollow fiber membrane dialyzers.

终末期肾病（ESRD）目前在美国每年造成约50,000人死亡。ESRD患者的数量正在逐渐增加，糖尿病和高血压是两个主要原因。这些患者的标准治疗是每周三次的终身血液透析（HD）治疗，但透析很难模拟自然肾功能。每周只有12小时的透析过滤血液是不符合生理的，也是不充分的。更频繁的透析是首选，因为它允许稳定的废物和液体清除，从而产生优越的代谢和血流动力学控制。据报道，当患者从典型的每周三次透析转为每日在家透析时，临床结果和生活质量都有显著改善。然而，每日透析的大规模实施是困难的。其中一些问题是患者无法或不愿在家进行透析，缺乏护士和技术人员在透析病房提供更多的治疗，以及政府付款人不愿承担更频繁的透析费用。2018年，仅CKD和ESRD患者的医疗保险支出就约为1200亿美元。为了应对这一巨大的健康和社会挑战，部件和系统的小型化以及在确保安全性的同时降低复杂性是透析研究和开发工作的核心。其中一个关键的障碍是当前膜技术的局限性。目前的膜模块体积庞大，需要一个由数米管道、泵和其他辅助部件组成的体外血液回路。建立每次透析的血液循环必须由一个合格的人来完成，这是一个主要的危险因素，阻碍了扩大家庭频繁透析和患者独立性的努力。为了解决患者的安全问题（通过减少/消除出血风险），提高美国和全世界的可负担性，并实现新的血管通道选择，在最近的R21项目中，我们已经纳米工程了一种新型膜，其渗透性比高通量商业膜高40倍。这种新膜具有优异的筛分性能，使透析器的尺寸突破性地缩小了两个数量级，从而可以直接连接到血管通道，从而消除了体外血液循环和泵（透析器可以仅使用动脉血压进行操作），减轻了对阻碍家庭透析发展的失血的恐惧。本研究的总体目标是评估新型高通量纳米膜微流控透析器模型的流体动力学性能，并评估相对于传统中空纤维膜透析器的流态差异。