The Complement System in Dialysis: A Forgotten Story?

Abstract

Significant advances have lead to a greater understanding of the role of the complement system within nephrology. The success of the first clinically approved complement inhibitor has created renewed appreciation of complement-targeting therapeutics. Several clinical trials are currently underway to evaluate the therapeutic potential of complement inhibition in renal diseases and kidney transplantation. Although, complement has been known to be activated during dialysis for over four decades, this area of research has been neglected in recent years. Despite significant progress in biocompatibility of hemodialysis (HD) membranes and peritoneal dialysis (PD) fluids, complement activation remains an undesired effect and relevant issue. Short-term effects of complement activation include promoting inflammation and coagulation. In addition, long-term complications of dialysis, such as infection, fibrosis and cardiovascular events, are linked to the complement system. These results suggest that interventions targeting the complement system in dialysis could improve biocompatibility, dialysis efficacy, and long-term outcome. Combined with the clinical availability to safely target complement in patients, the question is not if we should inhibit complement in dialysis, but when and how. The purpose of this review is to summarize previous findings and provide a comprehensive overview of the role of the complement system in both HD and PD.

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

“…Many factors lead to inflammation in HD patients such as biocompatibility of the dialyzer membrane [ 73 , 74 , 75 ], infection related to dialysis access [ 73 ], and impure dialysate containing cytokine-inducing substances labeled as endotoxins [ 73 , 76 ].…”

Challenges and Advances in Hemodialysis Membranes

“…The cascade continues into production of C5a and C5b-9 during the next stages of dialysis. As reported by Poppelaars et al [26] during a single session of hemodialysis, the level designated to C5b-9 and C3d/C3 ratios in plasma (measures of complement system activation) reaches up to 70%. However this has been interpreted as an underestimation of the measures values as they are only calculated for fluid phase, while solid phase (deposited complement system's element on the surface) is not considered.…”

“…Protein attachment to the surface is commonly studied under the title of displacement processes (Vroman effect) which might initiate the coagulation cascade [24,25]. Any adhered cell (or triggered cells by the surface) could be activated, which consequently results in cascade activation (autocatalytic enzymatic processes) of other cells through production of mediators (with various purposes ranging from hindering interfacial cell adherence to defensive system activation) [26]. Defensive system activation in hemodialysis reflects hemoincompatibility of the used polymeric membrane.…”

“…The reactions resulting in incompatibility are complex, and there are many unknown regions still to be covered; however, platelets, leukocytes, the complement, and the coagulation system are proven to be role players of this concept [26].…”

Dialysis membranes: A 2018 update

“…Complement activation: the contact of plasma with the dialysis membrane can result in complement activation, which can lead to a pseudo-anaphylactic reaction called complement activation-related pseudoallergy (CARPA). 36 It has been shown that complement activation is related to the progression of cardiovascular disease (CVD). According to several studies, patients with higher C3 levels are more likely to develop CV events.…”