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Author(s): Poppelaars F
Gaya Da Costa M
Faria B
Berger S
Assa S
Daha M
Medina Pestana J
Van Son W
Franssen C
Seelen M
Title: Intradialytic complement activation precedes the development of cardiovascular events in hemodialysis patients
Publisher: Frontiers Media
Issue Date: 2018
Abstract: Background: Hemodialysis (HD) is a life-saving treatment for patients with end stage renal disease. However, HD patients have markedly increased rates of cardiovascular morbidity and mortality. Previously, a link between the complement system and cardiovascular events (CV-events) has been reported. In HD, systemic complement activation occurs due to blood-to-membrane interaction. We hypothesize that HD-induced complement activation together with inflammation and thrombosis are involved in the development of CV-events in these patients. Methods: HD patients were followed for the occurrence of CV-events during a maximum follow-up of 45 months. Plasma samples were collected from 55 patients at different time points during one HD session prior to follow-up. Plasma levels of mannose-binding lectin, properdin and C3d/C3 ratios were assessed by ELISA. In addition, levels of von Willebrand factor, TNF-a and IL-6/IL-10 ratios were determined. An ex-vivo model of HD was used to assess the effect of complement inhibition. Results: During median follow-up of 32 months, 17 participants developed CV-events. In the CV-event group, the C3d/C3-ratio sharply increased 30 min after the start of the HD session, while in the event-free group the ratio did not increase. In accordance, HD patients that developed a CV-event also had a sustained higher IL-6/IL-10-ratio during the first 60 min of the HD session, followed by a greater rise in TNF-a levels and von Willebrand factor at the end of the session. In the ex-vivo HD model, we found that complement activation contributed to the induction of TNF-a levels, IL-6/IL-10-ratio and levels of von Willebrand factor. Conclusions: In conclusion, these findings suggest that early intradialytic complement activation predominantly occurred in HD patients who develop a CV-event during follow-up. In addition, in these patients complement activat was accompanied by a pro-inflammatory and pro-thrombotic response. Experimental complement inhibition revealed that this reaction is secondary to complement activation. Therefore, our data suggests that HD-induced complement, inflammation and coagulation are involved in the increased CV risk of HD patients.
Subject: Biocompatibility
Cardiovascular risk
Innate immunity
Source: Frontiers in Immunology, vol.9:2070
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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