Small Animal Hemodialysis with Ultrathin Silicon Nanomembranes

 描述(由申请人提供)：美国约有43万名终末期肾病(ESRD)患者接受血液透析(HD)，占所有医疗保险支出(340亿美元)的6%。家庭血液透析(HHD)既比中心内透析(ICHD)便宜，又能使患者更频繁地进行透析，因此对患者有利。尽管有这些好处，HHD的采用率很低(1.5%)，部分原因是与患者管理的透析相关的复杂性和安全性问题。这项提议将检验这样一种假设，即一种新型的高渗透透析膜技术(硅纳米膜)可以将血液透析所需的膜面积减少100倍。这样的突破可以通过使更小和可穿戴的设备、更短和更有效的透析时间以及更简单的系统显著改变透析格式来帮助推动HHD的采用。目标1将利用台式研究建立初步的最佳操作条件(流量、膜性能)，以最大限度地提高尿素清除率，同时达到理想的超滤率。目标2将使用目标1的工作台优化作为小动物研究(大鼠)的基线条件。通过饮食使大鼠患尿毒症，使用纳米膜的血液透析实验将再次确定尿素清除的最佳条件。研究还将测量中等重量的蛋白质清除、白蛋白保留、超滤以及细胞和蛋白质激活。所有结果将直接与传统HD膜的结果进行比较。如果治疗性减少尿素所需的膜表面积(KT/V=1.2)硅纳米膜比传统膜小100倍，我们的假设将得到支持。这些研究是由在非优化条件下进行的小动物模型中有希望的初步发现推动的。

 DESCRIPTION (provided by applicant): There are ~430,000 patients with End Stage Renal Disease (ESRD) in the US on hemodialysis (HD) accounting for > 6% of all Medicare spending ($34B). Home hemodialysis (HHD) is both less expensive than in-center dialysis (ICHD) and beneficial to patients because it enables more frequent dialysis. Despite these benefits HHD adoption is low (1.5%) in part because of the complexity and safety concerns associated with patient managed dialysis. This proposal will test the hypothesis that a novel, highly permeable dialysis membrane technology (silicon nanomembranes) can reduce the amount of membrane area required for hemodialysis 100 fold. Such a breakthrough can help drive the adoption of HHD by dramatically changing the format for dialysis by enabling smaller and wearable devices, shorter and more effective dialysis times, and simpler systems. Aim 1 will use bench top studies to establish a preliminary optimum operational conditions (flow rates, membrane properties) that maximize urea clearance while achieving ideal ultrafiltration rates. Aim 2 will use the bench top optimization from Aim 1 as a baseline condition for small animal studies (rats). Rats will be made uremic through diet and hemodialysis experiments with nanomembranes will again identify an optimum condition for urea clearance. Studies will also measure middle weight protein clearance, albumin retention, ultrafiltration and cellular and protein activation. All resuts will be compared directly to results with conventional HD membranes. Our hypothesis will be supported if the membrane surface area required for a therapeutic reduction of urea (KT/V = 1.2) is 100x less for silicon nano membranes than for conventional membranes. The studies are motivated by promising preliminary findings in a small animal model performed under non-optimized conditions.