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.

目前，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。这些患者的标准护理是每周三周终身血液透析（HD）治疗，但透析模仿天然肾功能。每周仅通过透析过滤血液12个小时，既是生理学的，也是不足的。更常见的是首选透析，因为它允许稳定的废物清除和流体清除，从而导致上代谢和血液动力学控制。随着患者从典型的每周三次转移到每天的透析中的一种，报道了临床结果和生活质量的显着改善。但是，很难大规模实施日常透析。其中一些是患者无法在家透析的情况下，护士和技术人员缺乏人员配备，无法在透析单位提供更多治疗方法，而政府付款人不愿承担更频繁的透析费用。 2018年，仅在CKD和ESRD患者上支出的医疗保险支出约为1,200亿美元。为了应对这一巨大的健康和社会挑战，组件和系统的小型化以及降低复杂性，同时确保安全是透析研究和发展工作的核心。关键障碍之一是当前膜技术的局限性。当前的膜模块是笨重的，需要一个由管道，泵和其他辅助成分组成的体外血回路。确定每个透析课程的血回路必须由合格的人进行，并提出主要的危险因素，以阻碍在房屋中扩大经常透析和患者独立性的努力。为了解决患者的安全问题（通过降低/消除出血风险），增强美国和世界各地的可用性，并在最近的R21项目下实现新的血管通道选项，我们对纳米工程进行了纳米工程的新膜，该新膜比高速浮游商业膜更易于渗透性。这款新膜表现出了出色的筛分性能，从而使透明剂的大小降低了两个数量级，因此可以直接连接到血管通道，从而消除了体外血回路和泵（可以使用动脉血压来操作透明剂，从而减轻人们对外来语言的恐惧，从而阻碍了疾病的增长。拟议的研究的总体目标是评估新的微流体透析模型的水力动力性能，用于新的高吞吐量纳米桥的保险，并评估相对于传统的空心纤维膜透析器，流动状态的差异。