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.
Highlights
An estimated 2.6 million people are treated for end-stage kidney disease (ESKD) worldwide [1]
There is no major difference in Abbreviations: AP, alternative pathway; C1-INH, C1 esterase inhibitor; C3aR, C3a-receptor; C5aR, C5a-receptor; C5a-receptor antagonists (C5aRA), C5a-receptor antagonist; complement activation-related pseudoallergy (CARPA), complement activation-related pseudo allergy; MCP, membrane cofactor protein; CD55, decay accelerating factor; CD59, membrane attack complex-inhibitory protein; CP, classical pathway; CR1, complement receptor 1; CR3, complement receptor 3; CRP, C-reactive protein; CV-event, cardiovascular event; DAF, decay accelerating factor; ESKD, end-stage kidney disease; HD, hemodialysis; IgG, immunoglobulin G; IgM, immunoglobulin M; IL, interleukin; LDL, low-density lipoprotein; LP, lectin pathway; MAC, membrane attack complex; MBL, mannose-binding lectin; MCP-1, monocyte chemoattractant protein-1; PD, peritoneal dialysis; sC5b-9, soluble C5b-9; sCR1, soluble complement receptor 1; TGF-β, tumor growth factor beta; TNF-α, tumor necrosis factor alfa
The latter is supported by the evidence that in C4-deficient patients, systemic complement activation and C3b deposition on the HD membrane are reduced during dialysis but not abolished [31]
Summary
Several clinical trials are currently underway to evaluate the therapeutic potential of complement inhibition in renal diseases and kidney transplantation. 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. 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.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
