1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.17
Figure 5 Model of innate immunity activation as a cause of cardiovascular disease during dialysis
Figure 5 | Model of innate immunity activation as a cause of cardiovascular disease during dialysis. a | During haemodialysis, the blood of the patient comes into prolonged contact with various biomaterials used in the haemodialysis circuits. This contact elicits bioincompatibility reactions, mainly owing to recognition of the biomaterial by the intravascular innate immune system. Activation of the cascade systems takes place on the surface of the tubing and dialysis membrane, as well as on the surfaces of gas bubbles produced by peristaltic pumps and gas traps. Proteins within the complement and coagulation systems bind to the non-biological surfaces, which triggers cascade system activation, leading to further protein deposition and clot formation. The adsorbed and conformationally changed proteins function as ligands for platelets and leukocytes (polymorphonuclear cells (PMNs) and monocytes) which are recruited, activated and bind to the surface. b | Soluble mediators produced during cascade system activation, such as C3a, C5a, soluble C5b–9 complex (sC5b–9), bradykinin and tissue factor (TF) as well as multiple cytokines and chemokines, are transported in the dialysis circuit back to the patient. The combined effect of these proinflammatory compounds and the relatively higher shear force in the tubing further activates platelets and leukocytes still present in the blood. c | Intravascular inflammation activates the patient's endothelium, resulting in loss of its anti-inflammatory and antithrombotic properties and the acquirement of a proinflammatory and prothrombotic phenotype. Increased expression of cell adhesion molecules such as E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) as well as release of von Willebrand Factor (vWF) promotes binding of activated platelets and leukocytes to the endothelial cell surface. Ultimately, these adverse reactions escalate resulting in repetitive systemic inflammation, and contribute to the generation of arteriosclerosis and cardiovascular disease in the patient. BKR2, bradykinin receptor 2; TM, thrombomodulin.
Ekdahl, K. N. et al. (2017) Cardiovascular disease in haemodialysis: role of the intravascular innate immune system
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