Development of continuous implantable renal replacement: past and future
Development of continuous implantable renal replacement: past and future
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DOI：
10.1016/j.trsl.2007.06.001
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发表时间：
2007-12-01
影响因子：
7.8
通讯作者：
Roy, Shuvo
中科院分区：
文献类型：
--
作者：
Fissell, William H.;Fleischman, Aaron J.;Roy, Shuvo
在美国，40多万肾衰竭患者中的大多数都需要在专门的透析中心接受3小时到5小时的透析治疗，通常是每周3次，但他们仍然患有加速的心血管疾病和感染。每天延长6至8小时的透析时间似乎与更好的结果有关，但会使透析网络不堪重负，并严重限制患者的活动。家庭透析小型化和自动化的技术将是为大多数透析患者提供延长日常透析所必需的。现有中空纤维聚合物膜的小型化受到循环和对流清除的高驱动压力要求的限制。基于微电子机械系统(MEMS)的膜技术的最新进展有望使可持续植入性肾脏替代疗法的发展成为可能。具有高度单分散孔径分布的硅纳米孔膜已经使用适合于低成本批量制造的协议来制造，类似于用于生产微电子产品的协议。对临界孔径在8-100 nm范围内的平板膜的水力渗透率进行了测量，证实了传统的流体传输模型对于植入式血液过滤器中液体流动的预测设计是足够准确的。通过与人近端小管细胞的体外生物相容性测试，发现硅没有细胞毒性，表现为形成具有紧密连接和中央纤毛的融合细胞层。过滤表征表明，纳米多孔膜表现出尺寸依赖的溶质截留，符合空间位阻模型。膜技术的这些进步从根本上使从中心透析系统到植入式透析系统的范式转变成为可能。
Most of the 400,000+ patients in the United States with kidney failure depend on dialysis treatments in dedicated dialysis centers for 3 h to 5 h, usually 3 times a week, but they still suffer from accelerated cardiovascular disease and infections. Extended daily dialysis, for 6 to 8 hours every day, seems to be associated with better outcomes but would overwhelm the dialysis networks and severely limit patient activity. Technology to miniaturize and automate home dialysis will be necessary to offer extended daily dialysis to most dialysis patients. Miniaturization of existing hollow-fiber polymer membranes is constrained by requirements for high driving pressures for circulation and convective clearance. Recent advances in membrane technology based on microelectromechanical systems (MEMS) promise to enable the development of continuous implantable renal replacement therapy. Silicon nanoporous membranes with a highly monodisperse pore size distribution have been produced using protocols amenable to low-cost batch fabrication similar to those used to produce microelectronics. Hydraulic permeability of the flat-sheet membranes with critical pore sizes in the range of 8-100 nm has been measured to confirm that conventional fluid transport models are sufficiently accurate for predictive design for bulk liquid flow in an implantable hemofilter. Membrane biocompatibility was tested in vitro with human proximal tubule cells and revealed that silicon does not exhibit cytotoxicity, as evidenced by the formation of confluent cell layers with tight junctions and central cilia. Filtration characterization demonstrated that the nanoporous membranes exhibit size-dependent solute rejection in agreement with steric hindrance models. These advances in membrane technology are fundamentally enabling for a paradigm shift from an in-center to implantable dialysis system.