Blood-incompatibility in haemodialysis: alleviating inflammation and effects of coagulation

Abstract

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.

Cerebral blood flow pulsatility and cerebral artery stiffness acutely decrease during hemodialysis

“…These reductions in regional arterial stiffness may in part result from decreased arterial BP, as BP is known to mechanically increase arterial stiffness. In addition, the reduction in stiffness could result from leukocyte activation as they come into contact with exogenous material from the dialysis membrane, releasing vasoactive mediators associated with vasodilation (Bowry et al, 2021 ). This hypothesis, however, was not directly tested in our study.…”

Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF)

“…The cause of inflammation in hemodialysis is multifactorial, and may originate from several sides. Repetitive contact of blood mononuclear cells with dialysis tubes and dialyzer membranes having insufficient biocompatibility may induce inflammation [ 23 , 24 , 25 ]. Complement activating membranes (e.g., cuprophan made membranes) induced the expression of IL-1β and of complement factor 5a (C5a) [ 23 , 26 ].…”

The use of a low-flux hemo-dialyzer is associated with impaired platelet aggregation in patients undergoing chronic hemodialysis

“…[ 24 , 25 ] Platelet activation is reported to be a component of dialysis biocompatibility. [ 15 ] Aggarwal et al [ 4 ] found continued dialysis decreased platelet activity using flow cytometry to investigate platelet function. The bio-incompatibility character of a low-flux dialyzer may exhaust the platelet more during dialysis and resulted in post-dialytic CEPI prolongation.…”