Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames St, Cambridge, MA, 02142, USA.
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.
Ann Biomed Eng. 2024 Mar;52(3):526-541. doi: 10.1007/s10439-023-03397-6. Epub 2023 Nov 22.
Inadequate clearance of protein-bound uremic toxins (PBUTs) during dialysis is associated with morbidities in chronic kidney disease patients. The development of high-permeance membranes made from materials such as graphene raises the question whether they could enable the design of dialyzers with improved PBUT clearance. Here, we develop device-level and multi-compartment (body) system-level models that account for PBUT-albumin binding (specifically indoxyl sulfate and p-cresyl sulfate) and diffusive and convective transport of toxins to investigate how the overall membrane permeance (or area) and system parameters including flow rates and ultrafiltration affect PBUT clearance in hemodialysis. Our simulation results indicate that, in contrast to urea clearance, PBUT clearance in current dialyzers is mass-transfer limited: Assuming that the membrane resistance is dominant, raising PBUT permeance from 3 × 10 to 10 m s (or equivalently, 3.3 × increase in membrane area from ~ 2 to ~ 6 m) increases PBUT removal by 48% (from 22 to 33%, i.e., ~ 0.15 to ~ 0.22 g per session), whereas increasing dialysate flow rates or adding adsorptive species have no substantial impact on PBUT removal unless permeance is above ~ 10 m s. Our results guide the future development of membranes, dialyzers, and operational parameters that could enhance PBUT clearance and improve patient outcomes.
在透析过程中，蛋白质结合尿毒症毒素 (PBUT) 的清除不足与慢性肾脏病患者的发病率有关。由石墨烯等材料制成的高通量膜的发展提出了一个问题，即它们是否能够设计出具有改善 PBUT 清除率的透析器。在这里，我们开发了设备级和多腔（体）系统级模型，这些模型考虑了 PBUT-白蛋白结合（特别是吲哚硫酸酯和对甲酚硫酸盐）以及毒素的扩散和对流传输，以研究整体膜通透性（或面积）和系统参数（包括流速和超滤）如何影响血液透析中的 PBUT 清除率。我们的模拟结果表明，与尿素清除率不同，当前透析器中的 PBUT 清除率受传质限制：假设膜阻力占主导地位，将 PBUT 通透性从 3×10 提高到 10 m s（或等效地，将膜面积从2 增加到6 m）将 PBUT 去除率提高 48%（从 22%提高到 33%，即每次透析从0.15 提高到0.22 g），而增加透析液流速或添加吸附物质除非通透性高于~10 m s，否则对 PBUT 去除率没有实质性影响。我们的结果指导了未来的膜、透析器和操作参数的发展，这些发展可以提高 PBUT 的清除率并改善患者的预后。
