Proteomic profiling of blood‐dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis‐induced inflammatory response

Mareš, J; Richtrova, Pavlina; Hricinova, Alena; Tůma, Zdeněk; Moravec, Jiřı́; Lysák, Daniel; Matějovič, Martin

doi:10.1002/prca.201000031

Cited by 48 publications

(62 citation statements)

References 40 publications

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“…Therefore, lower levels of vitronectin or clusterin may be expected to result in the formation of relatively less SC5b-9. Both vitronectin and clusterin have been shown to be adsorbed onto the surface of dialysis membranes [26,27,28] and, in the case of vitronectin, correlate negatively with the length of time on dialysis [29]. These complexities highlight the difficulties in interpreting SC5b-9 levels in relation to complement activation.…”

Section: Discussionmentioning

confidence: 99%

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Lines

Richardson²,

Thomas

et al. 2015

Nephron

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Background: Patients on haemodialysis (HD) have high rates of cardiovascular (CV) disease and activation of the complement system. Despite evidence in non-renal patients that these may be linked, this association has received little attention in HD patients to date. In the setting of a randomised controlled trial we evaluated the relationships between baseline complement levels and subsequent CV events and mortality, in addition to the effects of HD with a vitamin E (VE)-coated dialysis membrane on circulating complement levels. Methods: A total of 260 HD patients were randomised to dialysis with a VE-coated dialysis membrane or non-VE coated equivalent for 12 months. Blood samples were taken at baseline, 6 and 12 months for measurement of C3, factor D, factor H and SC5b-9 levels. Data were collected prospectively on deaths and CV events. Results: Higher C3 levels at baseline were associated with subsequent CV events (hazard ratio 1.20 (1.01-1.42) per 0.1 mg/ml). Patients with intermediate SC5b-9 levels had significantly lower CV event rates and mortality than those with either high or low levels (p < 0.01). There were no effects of the VE-membranes on the complement components measured nor the clinical endpoints considered. Conclusions: The levels of C3 and SC5b-9 may have prognostic utility for predicting future CV events and/or mortality in HD patients - a relationship that requires further investigation. Dialysing prevalent HD patients with VE-bonded polysulfone membranes for a period of 12 months did not alter the circulating levels of the alternative complement pathway components considered here.

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Section: Discussionmentioning

confidence: 99%

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Lines

Richardson²,

Thomas

et al. 2015

Nephron

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“…In that way, the dialyzer membrane may entrap on the blood surface solutes that reach high relative concentrations to become more available for the interaction with blood cell receptors and plasma proteins. These may result in untoward reactions and activation processes such as those described for components of the complement and coagulation pathways [4]. …”

Section: Introduction: the Road From Biocompatibility To Bioactivitymentioning

confidence: 99%

“…Accordingly, the repeated contact of patient’s blood with the materials of the extracorporeal circulation causes oxidative stress biomarker formation, changes in the levels of inflammatory and anti-inflammatory cytokines (such as IFN-γ, TNF-α, interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12 and IL-18), acute-phase (C-reactive protein (CRP), SSA and fibrinogen) and negative-phase (serum albumin, prealbumin and transferrin) proteins, and leukocyte subsets, which reset to a dysfunctional immunoinflammatory phenotype [recently reviewed in [7]]. Other consequences of bioincompatibility are the activation of complement and contact pathways [4,8], and platelets [9]. Indices of red blood cell damage can represent other useful markers of biocompatibility [7,10,11].…”

Section: Introduction: the Road From Biocompatibility To Bioactivitymentioning

confidence: 99%

Vitamin E as a Functional and Biocompatibility Modifier of Synthetic Hemodialyzer Membranes: An Overview of the Literature on Vitamin E-Modified Hemodialyzer Membranes

et al. 2012

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Along with one century of history, research has provided many solutions for hemodialysis (HD) biomaterials, encompassing several generations of copolymers that have found wide application in the development of hollow-fiber dialyzer membranes. Polysulfone-based biomaterials have gained increasing consideration and are now the gold standard in the production of biocompatible hemodialyzers. However, even the highest biocompatibility now available cannot exclude that dialyzer membranes and the overall extracorporeal circulation may produce at the subclinical level immunoinflammatory reactions and thus an increased cardiovascular risk of patients on regular HD therapy. The lipophilic antioxidant and radical scavenger vitamin E has been used (as α-tocopherol) to modify cellulosic and synthetic hollow-fiber membranes with the ultimate goal to neutralize harmful reactive species and to mimic lipid structures of blood cell plasmalemma and lipoprotein particles. Besides filtration and biocompatibility, this modifier has introduced a third function of dialyzer membranes, namely ‘antioxidant bioactivity’. Vitamin E can also serve as a template molecule to produce synthetic redox-active and -silent (non-antioxidant) modifiers for future generations of dialyzer membranes. This mini-review article describes the evolution of vitamin E-derived copolymers as a generation of biomaterials that has offered a clinical challenge and still represents a chance to further improving the quality of HD therapy.

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“…The latter phenomenon is linked to leukocyte apoptosis and impaired phagocytosis [37], impaired antigen presentation function [38,39], and increased cytokine production [7]. Dialytic treatment may activate antibodies and complements; indeed, dialyzers absorb albumin, complement component 3 (C3), C1q, immunoglobulin G and ficolin, leading to activation of the alternative [9,40], classical, and lectin [41] pathways of complement. All these alterations in innate immunity unavoidably have affects in adaptive immunity as well, inducing elevated number of high IL-2-producing T-cells [27], low number of B-lymphocytes (due to apoptosis) [42], dysfunctional memory CD4 + T-cells [43], reduced CD4/CD8 ratio, increased Th1/Th2 ratio, and depletion of memory CD4 and CD8 T-cells and regulatory T-cells (Tregs; more likely to exhibit an IL-17 pro-inflammatory phenotype) [44].…”

Section: Adaptive and Innate Immunity Abnormalities In Esrdmentioning

confidence: 99%

Targeting Immunity in End-Stage Renal Disease

2017

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Background: Despite the stable incidence of end-stage renal disease (ESRD), it continues to be associated with an unacceptably high cardiovascular risk. Summary: ESRD is characterized by enhanced oxidative stress and severe inflammation, which boost cardiovascular risk, thus increasing cardiovascular-associated mortality rate. While substantial effort has been made in the technological innovation of dialytic techniques, few significant advances have been made to reduce inflammation in patients with ESRD. Indeed, this contrasts with the extensive scientific breakthroughs made in the basic field of science in targeting inflammation. There is thus a pressing need for clinical trials to test the effect of reducing inflammation in patients with ESRD. Here, we will revisit the negative effect of ESRD on inflammation and explore the impact of enhanced inflammation on cardiovascular outcomes and survival in patients with ESRD. Finally, we will discuss the need for clinical trials that target inflammation in ESRD, as well as weigh potential disadvantages and offer novel innovative approaches. Key Message: We will try to understand why the issue of inflammation has not been successfully addressed thus far in patients with ESRD, while at the same time weighing the potential disadvantages and offering novel innovative approaches for targeting inflammation in patients with ESRD.

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Proteomic profiling of blood‐dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis‐induced inflammatory response

Abstract: ficolin-2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis-induced leukopenia, and results in a significant depletion of ficolin-2, an essential component of innate immunity.

Cited by 48 publications

References 40 publications

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Complement and Cardiovascular Disease - The Missing Link in Haemodialysis Patients?

Vitamin E as a Functional and Biocompatibility Modifier of Synthetic Hemodialyzer Membranes: An Overview of the Literature on Vitamin E-Modified Hemodialyzer Membranes

Targeting Immunity in End-Stage Renal Disease

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