Novokhodko Alexander, Du Nanye, Hao Shaohang, Wang Ziyuan, Shu Zhiquan, Ahmad Suhail, Gao Dayong
Mechanical Engineering, University of Washington (Seattle), 3900 E Stevens Way NE, Seattle, WA 98195-0001, USA.
School of Engineering and Technology, University of Washington (Tacoma), 1900 Commerce Street, Tacoma, WA 98402-3100, USA.
Bioengineering (Basel). 2024 Dec 12;11(12):1262. doi: 10.3390/bioengineering11121262.
Liver failure is the 12th leading cause of death worldwide. Protein-bound toxins such as bilirubin are responsible for many complications of the disease. Binder dialysis systems use albumin or another binding molecule in dialysate and detoxifying sorbent columns to remove these toxins. Systems like the molecular adsorbent recirculating system and BioLogic-DT have existed since the 1990s, but survival benefits in randomized controlled trials have not been consistent. New binder dialysis systems, including open albumin dialysis and the Advanced Multi-Organ Replacement system, are being developed. Optimal conditions for binder dialysis have not been established. We developed and validated a computational model of bound solute dialysis. It predicted the impact of changing between two test setups using different polysulfone dialyzers (F3 and F6HPS). We then predicted the impact of varying the dialysate flow rate on toxin removal. We found that bilirubin removal declines with dialysate flow rate. This can be explained through a linear decline in free bilirubin membrane permeability. Our model quantifies this decline through a single parameter (polysulfone dialyzers). Validation for additional dialyzers and flow rates will be needed. This model will benefit clinical trials by predicting optimal dialyzer and flow rate conditions. Accounting for toxin adsorption onto the dialyzer membrane may improve results further.
肝衰竭是全球第12大致死原因。胆红素等与蛋白质结合的毒素是该疾病许多并发症的成因。结合剂透析系统在透析液中使用白蛋白或其他结合分子以及解毒吸附柱来清除这些毒素。自20世纪90年代以来就有分子吸附循环系统和BioLogic-DT等系统，但随机对照试验中的生存获益并不一致。包括开放式白蛋白透析和高级多器官替代系统在内的新型结合剂透析系统正在研发中。结合剂透析的最佳条件尚未确定。我们开发并验证了一种结合溶质透析的计算模型。它预测了使用不同聚砜透析器（F3和F6HPS）在两种测试设置之间切换的影响。然后我们预测了改变透析液流速对毒素清除的影响。我们发现胆红素清除率随透析液流速下降。这可以通过游离胆红素膜通透性的线性下降来解释。我们的模型通过一个单一参数（聚砜透析器）对这种下降进行量化。还需要对其他透析器和流速进行验证。该模型将通过预测最佳透析器和流速条件使临床试验受益。考虑毒素在透析器膜上的吸附可能会进一步改善结果。
