在血液透析中有效清除高磷血症患者血磷的稀土结合剂

Aiming at the challenge that it is diffcult to remove and control serum phosphates effectively in hemodialysis treatment for the renal failure patients with hyperphosphatemia, we put forward a research project that can safely and effectively clear the serum phosphate in hemodialysis by means of the rare earth sorbent with micro- and nano-structure as phosphate binder added into the dialysis solution based on characterics of high selective binding affinity for phosphates, low toxicity and safety, and excretion pathway through liver metabolism of rare earth ions like La3+. The major research contents include: (1) To designedly synthesize and screen out the rare earth phosphate binders with micro- and nano-structures for effective clearance of the serum phosphate in hemodialysis, and to characterize their compositions, morphologies, surface structures, particle sizes, and so on; (2) To investigate the serum phosphorus removal performance such as adsorption capacity, adsorption efficiency, adsorption rate and the influencing factors (i.e. toxins in the plasma, biological molecules and the electrolyte ions in dialysis solution, etc.), and to explore and discuss the reaction mechanism of the serum phosphorus clearance; (3) To evaluate or estimate their safety. The major research objective is to obtain new rare earth phosphate binders with efficient, fast and safe, which may be used for the treatment of hyperphosphatemia in hemodialysis. The research achievements will elucidate the effect and mechanism of phosphorus removal of the rare earth bonders in hemodialysis treatment, can provide new ideas and ways for the clinical treatment of hyperphosphatemia, have huge potential for clinical application and potential social and economic benefits.

针对高磷血症的肾衰患者血液透析治疗对血磷难以有效清除和控制的挑战，基于镧等稀土离子对磷酸根的高选择性亲和作用、低毒安全性和肝脏代谢排泄途径等特点，我们提出了一个使用微纳米结构稀土吸附剂作为磷结合剂添加到透析液中进行安全有效清除血磷的研究项目。其主要内容包括：（1）设计合成并筛选出可在血液透析中用于血磷的有效清除的微纳米结构稀土磷结合剂，表征其组成、形貌、表面结构和粒子大小等特性；（2）评价其除血磷性能（如吸附容量、吸附效率和吸附速率等）和影响因素（如血浆中的毒素、生物分子和透析液中电解质离子等），探讨其除血磷反应机理；（3）评估其安全性。主要研究目标是：获得在血液透析中可以用于高磷血症治疗的高效、快速和安全的新型微纳米结构稀土磷结合剂。该研究成果将阐明稀土结合剂在血液透析治疗中的除磷效果和除磷机理，能够为高磷血症的临床治疗提供新的思路和途径，具有巨大的临床应用潜力和潜在的社会及经济效益。

高磷血症严重威胁患者的生命健康，但患者在血液透析治疗中难以对血磷进行有效清除和控制。本项目基于镧等稀土离子对磷酸根的高选择性亲和作用、低毒安全性和肝脏代谢排泄途径等特点，设计合成微纳米结构稀土吸附剂作为磷结合剂添加到透析液中进行安全有效清除血磷的研究。其完成的主要工作有：(1)设计合成了多种微纳米结构稀土磷结合剂(如RE2O3和CeO2纳米粒子，Ln(OH)3纳米棒，Y4O(OH)9(NO3)纳米棒和四方形纳米片等)，表征其组成、形貌、表面结构和粒子大小等特性；(2)评价了除血磷性能(如吸附容量、吸附效率和吸附速率等)和影响因素(如血浆中的毒素、生物分子和透析液中电解质离子等)，探讨了除血磷反应机理；(3)评估了安全性。研究结果表明，设计合成的稀土磷结合剂在血液透析器中能够快速有效地清除血液或血浆中的无机磷酸根离子，静电吸附和离子交换是其主要的除磷机理，其安全性的初步评估结果风险不高。进一步的实验结果证明，血液透析除磷动力学曲线决定步骤是组织和细胞的磷(组织和细胞中的磷>70%以上，而血浆中的磷<1%)渗透到血液中的速度。因此，通过稀土磷结合剂来提高除磷效率非常有限，甚至没有必要。不过，我们发现这些稀土磷结合剂在磷酸化肽富集和环保领域中的应用潜力巨大和前景广阔。