Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients

Buraczyńska, Monika; Ksiazek, Piotr; Waciński, Piotr; Żukowski, Paweł; Drăgan, M; Bednarek-Skublewska, Anna

doi:10.1016/j.humimm.2010.06.001

Cited by 10 publications

(11 citation statements)

References 31 publications

(34 reference statements)

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“…It has been hypothesized that complement activation leads to HD-induced inflammation and thereby increases the subsequent cardiovascular risk ( 4 ). In accordance, several studies have shown an association between complement and cardiovascular events (CV-event) ( 8 , 11 – 14 ). However, the link between complement activation products and CV-events remains poorly characterized ( 15 ).…”

Section: Introductionsupporting

confidence: 70%

“…Despite significant advances in the biocompatibility of HD membranes, complement activation remains an undesired but relevant issue ( 8 , 15 ). Higher levels of complement components as well as loss of complement inhibitors have been associated with a higher risk for cardiovascular disease in HD patients ( 8 , 11 – 14 ). Recently, complement activation prior to a HD session was associated with the occurrence of CV-events in HD patients ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

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Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients

et al. 2018

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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-α 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-α 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-α 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 activation 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.

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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients

et al. 2018

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“…Furthermore, several studies have demonstrated that CRP levels in HD patients are associated to cardiovascular mortality ( 50 – 52 ). Buraczynska et al revealed that in HD patients the complement receptor 1 (CR1) gene polymorphism C5507G is independently associated with the susceptibility for cardiovascular disease ( 46 ). Whether this effect is mediated via the complement inhibitory capacity of CR1 or via the recently discovered function of CR1 in the binding and clearance of native LDL remains to be elucidated ( 53 ).…”

Section: Hemodialysismentioning

confidence: 99%

The Complement System in Dialysis: A Forgotten Story?

et al. 2018

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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.

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“…To date, two previous studies have investigated the relationship between CR1 polymorphisms and cardiovascular risk. Buraczynska et al found that the GG phenotype of the Pro1827Arg polymorphism, corresponding to decreased erythrocyte-CR1 expression [23,32], was more prevalent in end-stage renal disease patients with a history of cardiovascular disease than in those without cardiovascular disease [33]. In contrast, Boiocchi et al described a lower prevalence of the GG variant in hypercholesterolemic patients with a history of coronary artery disease than in healthy controls [34].…”

Section: Discussionmentioning

confidence: 99%

Complement receptor 1 gene polymorphisms are associated with cardiovascular risk

et al. 2017

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Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients

Cited by 10 publications

References 31 publications

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients

The Complement System in Dialysis: A Forgotten Story?

Complement receptor 1 gene polymorphisms are associated with cardiovascular risk

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