Bowry Sudhir K, Kircelli Fatih, Himmele Rainer, Nigwekar Sagar U
Dialysis-at-Crossroads (D@X) Advisory, Bad Nauheim, Germany.
Global Medical Information and Education, Fresenius Medical Care, Bad Homburg, Germany.
Clin Kidney J. 2021 Dec 27;14(Suppl 4):i59-i71. doi: 10.1093/ckj/sfab185. eCollection 2021 Dec.
Blood-incompatibility is an inevitability of all blood-contacting device applications and therapies, including haemodialysis (HD). Blood leaving the environment of blood vessels and the protection of the endothelium is confronted with several stimuli of the extracorporeal circuit (ECC), triggering the activation of blood cells and various biochemical pathways of plasma. Prevention of blood coagulation, a major obstacle that needed to be overcome to make HD possible, remains an issue to contend with. While anticoagulation (mainly with heparin) successfully prevents clotting within the ECC to allow removal of uraemic toxins across the dialysis membrane wall, it is far from ideal, triggering heparin-induced thrombocytopenia in some instances. Soluble fibrin can form even in the presence of heparin and depending on the constitution of the patient and activation of platelets, could result in physical clots within the ECC (e.g. bubble trap chamber) and, together with other plasma and coagulation proteins, result in increased adsorption of proteins on the membrane surface. The buildup of this secondary membrane layer impairs the transport properties of the membrane to reduce the clearance of uraemic toxins. Activation of complement system-dependent immune response pathways leads to leukopenia, formation of platelet-neutrophil complexes and expression of tissue factor contributing to thrombotic processes and a procoagulant state, respectively. Complement activation also promotes recruitment and activation of leukocytes resulting in oxidative burst and release of pro-inflammatory cytokines and chemokines, thereby worsening the elevated underlying inflammation and oxidative stress condition of chronic kidney disease patients. Restricting all forms of blood-incompatibility, including potential contamination of dialysis fluid with endotoxins leading to inflammation, during HD therapies is thus still a major target towards more blood-compatible and safer dialysis to improve patient outcomes. We describe the mechanisms of various activation pathways during the interaction between blood and components of the ECC and describe approaches to mitigate the effects of these adverse interactions. The opportunities to develop improved dialysis membranes as well as implementation strategies with less potential for undesired biological reactions are discussed.
血液不相容性是所有血液接触装置应用和治疗（包括血液透析（HD））中不可避免的情况。离开血管环境和内皮保护的血液会面临体外循环（ECC）的多种刺激，从而触发血细胞的激活和血浆的各种生化途径。预防血液凝固是使血液透析成为可能需要克服的主要障碍，仍然是一个需要应对的问题。虽然抗凝（主要使用肝素）成功地防止了ECC内的凝血，从而允许通过透析膜壁清除尿毒症毒素，但它远非理想，在某些情况下会引发肝素诱导的血小板减少症。即使在存在肝素的情况下也可能形成可溶性纤维蛋白，并且根据患者的体质和血小板的激活情况，可能会在ECC内（如气泡捕捉室）形成物理凝块，并且与其他血浆和凝血蛋白一起，导致蛋白质在膜表面的吸附增加。这种二级膜层的积累会损害膜的传输特性，从而降低尿毒症毒素的清除率。补体系统依赖性免疫反应途径的激活分别导致白细胞减少、血小板 - 中性粒细胞复合物的形成以及组织因子的表达，从而分别促成血栓形成过程和促凝状态。补体激活还促进白细胞的募集和激活，导致氧化爆发以及促炎细胞因子和趋化因子的释放，从而使慢性肾病患者潜在的炎症和氧化应激状况恶化。因此，在血液透析治疗期间限制所有形式的血液不相容性，包括透析液被内毒素污染导致炎症的可能性，仍然是实现更血液相容和更安全透析以改善患者预后的主要目标。我们描述了血液与ECC组件相互作用期间各种激活途径的机制，并描述了减轻这些不良相互作用影响的方法。还讨论了开发改进的透析膜的机会以及具有较少不良生物反应可能性的实施策略。
