Taming hemodialysis-induced inflammation: Are complement C3 inhibitors a viable option?

Abstract

Owing to an increasing shortage of donor organs, the majority of patients with end-stage kidney disease remains reliant on extracorporeal hemodialysis (HD) in order to counter the lifelong complications of a failing kidney. While HD remains a life-saving option for these patients, mounting evidence suggests that it also fuels a vicious cycle of thromboinflammation that can increase the risk of cardiovascular disease. During HD, blood-borne innate immune systems become inappropriately activated on the biomaterial surface, instigating proinflammatory reactions that can alter endothelial and vascular homeostasis. Complement activation, early during the HD process, has been shown to fuel a multitude of detrimental thromboinflammatory reactions that collectively contribute to patient morbidity. Here we discuss emerging aspects of complement's involvement in HD-induced inflammation and put forth the concept that targeted intervention at the level of C3 might constitute a promising therapeutic approach in HD patients.

• Authors: Dimitrios C Mastellos, Edimara S Reis, Ali-Reza Biglarnia, Meryl Waldman, Richard J Quigg, Markus Huber-Lang, Marc A Seelen, Mohamed R Daha, John D Lambris
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 198 Pg. 102-105 (01 2019) ISSN: 1521-7035 [Electronic] United States
• PMID: 30472267 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Complement C3
• Complement Inactivating Agents

Topics

• Complement C3 (antagonists & inhibitors)
• Complement Inactivating Agents (therapeutic use)
• Humans
• Inflammation (drug therapy)
• Renal Dialysis (adverse effects)