Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden.
Linnæus Center of Biomaterials Chemistry, Linnæus University, SE-391 82 Kalmar, Sweden.
Nat Rev Nephrol. 2017 May;13(5):285-296. doi: 10.1038/nrneph.2017.17. Epub 2017 Feb 27.
Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.
血液透析是终末期肾病患者的一种救命性肾脏替代疗法，但这种疗法也对血管固有免疫系统构成了重大挑战，血管固有免疫系统由补体、接触和凝血系统组成。慢性炎症与血液透析患者的心血管疾病（CVD）密切相关。在血液透析过程中，血浆级联系统中的蛋白质会发生生物材料诱导的接触激活，最初会导致生物材料表面局部产生炎症介质。炎症通过可溶性激活产物和在血液透析过程中产生的介质传播，并与激活的白细胞和血小板一起通过体外回路输送回患者体内。其综合作用会激活心血管系统的内皮，内皮会失去抗血栓和抗炎特性，从而导致动脉粥样硬化形成和动脉硬化。这一概念表明，需要最大限度地抑制血管固有免疫系统，以降低血液透析患者患 CVD 的风险。实现这一目标的一种潜在方法是用针对多个血管级联系统的广谱系统性药物治疗患者。或者，可以在血液透析回路中使用引起最小级联系统激活的“隐身”生物材料。
