维持性血液透析患者蛋白结合尿毒症毒素清除动力学模型的研究

Study on the kinetic model of the clearance of protein-bound uremic toxins in maintenance hemodialysis patients

目的通过构建维持性血液透析患者蛋白结合尿毒症毒素(protein-bound uremic toxins, PBUTs)的透析清除动力学模型, 评估向透析液中添加不同吸附能力的吸附剂对PBUTs清除率的影响, 并且运用此模型预测吸附剂的吸附效能。方法该研究将血浆流速(Qp)、透析液流速(Qd)、PBUTs血浆游离分数(f1)、PBUTs透析液游离分数(f2)、透析器传质系数(K)和透析膜表面积(A)的参数综合, 通过透析过程的质量平衡方程和菲克第一定律(Fick''s first law)构建透析器中的PBUTs吸附清除的动力学数学模型, 并运用此模型评估不同PBUTs清除率与透析器参数和吸附剂吸附能力的变化关系。结果该研究的PBUTs吸附清除的动力学数学模型:PBUTs清除率(CL)=Qp1-f1-f2γφf1-f2γ,γ=QpQd,φ=eKAf1Qp-f2Qd。应用该模型对硫酸吲哚酚(indoxyl sulfate, IS)和对甲酚硫酸盐(p-cresol sulfate, pCS)透析过程的透析参数分析发现, PBUTs清除率随其在血浆中与白蛋白结合能力降低、透析器中血浆流速升高、透析液流速升高、透析器传质能力增强、透析膜表面积增大及透析液中吸附剂的吸附能力增强而升高, 并且升高趋势在应用吸附剂后尤为明显;进一步分析透析液流速和透析液中吸附剂吸附能力发现, 透析液流速升高可以弥补透析液中吸附剂吸附能力的差异, 在透析液流速趋于无限情况下, 透析液中吸附剂的吸附能力对PBUTs清除率没有影响。结论在透析过程中向透析液中添加PBUTs吸附剂能够明显提高PBUTs的透析清除率, 具有临床应用价值。

Objective A kinetic model of the clearance of protein-bound uremic toxins(PBUTs)in maintenance hemodialysis patients is established to evaluate the effects of adding sorbents with different sorption efficiency to dialysate on the clearance rate of PBUTs,and to predict the sorption efficiency of sorbents using the model.Methods The kinetic model was established by integrating the parameters of plasma flow rate(Qp),dialysate flow rate(Qd),free plasma fraction of PBUTs(f1),free dialysate fraction of PBUTs(f2),mass transfer coefficient of dialyzer(K)and surface area of dialysis membrane(A),and using the mass balance equation and Fick's first law.The model was also used to evaluate the relationship between the clearance rate of different PBUTs and the parameters of dialyzer and the sorption efficiency of sorbents.Results The kinetic model of PBUTs clearance(CL):CL=Qp(1−f1−f2γφf1−f2γ),γ=QpQd,φ=eKA(f1Qp−f2Qd).The model was used to analyze the dialysis parameters of indoxyl sulfate and p-cresol sulfate dialysis.The clearance rate of PBUTs increased with the decrease of its binding capacity to albumin in plasma and the increase of plasma flow rate in dialyzer,dialysate flow rate,mass transfer coefficient of dialyzer,surface area of dialysis membrane,and sorption capacity of sorbents in dialysate.The increasing trend of PBUTs clearance rate was particularly obvious after applying sorbents.Further analysis of the dialysate flow rate and the sorption efficiency of sorbents in the dialysate showed that the increase of the dialysate flow rate could make up for the difference of the sorption efficiency of sorbents.When the dialysate flow rate tended to be infinite,the sorption efficiency of sorbents in the dialysate had no effect on the clearance rate of PBUTs.Conclusion Adding sorbents of PBUTs to the dialysate during dialysis can significantly improve the clearance rate of PBUTs,suggesting a promising clinical application value.