Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review

Skinner, Sarah; Derebail, Vimal K.; Poulton, Caroline J.; Bunch, Donna C.; Roy‐Chaudhury, Prabir; Key, Nigel S.

doi:10.1016/j.xkme.2021.04.006

Cited by 15 publications

(11 citation statements)

References 119 publications

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“…While the cleavage of kininogen generates bradykinin, stimulating the release of proinflammatory cytokines [23,24], the coagulative pathway is amplified by the activation of the factor IX, which binds the activated factor VIII and factor X, leading to the production of thrombin and then to fibrin generation and platelet activation [25,26].…”

Section: Platelets and Coagulation Systemmentioning

confidence: 99%

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

Campo

Lacquaniti

Trombetta

et al. 2022

JCM

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Biocompatibility in hemodialysis (HD) has considerably improved in recent decades, but remains an open issue to be solved, appearing essential to reduce systemic inflammation and enhance patients’ clinical outcomes. Clotting prevention, reduction in complement and leukocyte activation, and improvement of antioxidant effect represent the main goals. This review aims to analyze the different pathways involved in HD patients, leading to immune system dysfunction and inflammation. In particular, we mostly review the evidence about thrombogenicity, which probably represents the most important characteristic of bio-incompatibility. Platelet activation is one of the first steps occurring in HD patients, determining several events causing chronic sub-clinical inflammation and immune dysfunction involvement. Moreover, oxidative stress processes, resulting from a loss of balance between pro-oxidant factors and antioxidant mechanisms, have been described, highlighting the link with inflammation. We updated both innate and acquired immune system dysfunctions and their close link with uremic toxins occurring in HD patients, with several consequences leading to increased mortality. The elucidation of the role of immune dysfunction and inflammation in HD patients would enhance not only the understanding of disease physiopathology, but also has the potential to provide new insights into the development of therapeutic strategies.

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Section: Platelets and Coagulation Systemmentioning

confidence: 99%

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

Campo

Lacquaniti

Trombetta

et al. 2022

JCM

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“…Complement is an important part of the innate immune system, and their defects, dysfunction, and abnormal activation are involved in the occurrence and development of a variety of diseases ( Freiwald and Afzali, 2021 ). The complement system is a highly complex biological reaction system that is activated by the classical pathway, alternative pathway, or lectin pathway ( Skinner et al, 2021 ). During the activation process, multiple active fragments are produced, which can mediate a variety of biological effects.…”

Section: Discussionmentioning

confidence: 99%

Locally generated C3 regulates the clearance of Toxoplasma gondii by IFN-γ-primed macrophage through regulation of xenophagy

et al. 2022

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Exogenous pathogen infection can induce autophagy in cells. Autophagy is essential for cell survival, development, and homeostasis. It not only regulates cell defense and stress, but also has a close relationship with innate and adaptive immunity. Complement is an important part of innate immunity, which could be activated by three approaches, including classic, alternative, and lectin pathways. All the three pathways result in the activation of C3, and generate anaphylatoxin fragments C3a and C5a, and formation of the membrane attack complex. Either C3a or C5a induces the inflammatory cytokines through binding to C3aR or C5aR, respectively. However, it is still unknown whether the complement could regulate the autophagy of intracellular microorganisms or not. In this study, we constructed a Toxoplasma gondii (T. gondii) and macrophages co-culture experimental model using T. gondii expressing enhanced green fluorescence protein (EGFP) fluorescence and C3−/-C57BL/6 J mice for that T. gondii invaded peritoneal macrophages in mice. Western blot, laser confocal microscopy (LCM), and transmission electron microscopy (TEM) were used to observe the changes of autophagy between the macrophages from wild-type (WT) and C3−/− mice. Flow cytometry and LCM were used to investigate the effect of autophagy on the killing ability of macrophages against T. gondii. Here, we found that local C3 could suppress not only the canonical autophagy of macrophage, but also the xenophagy to T. gondii. Interestingly, the inhibition of C3 on host cell autophagy could significantly suppress the clearance of T. gondii by the IFN-γ-primed macrophage. Finally, we investigated the mechanism of the autophagy regulation of C3 that the effect of C3 on the macrophage-specific autophagy against T. gondii depends on mTOR. And, there is C3a but not C5a/C5aR involved in regulating macrophage xenophagy against T. gondii. Collectively, our findings suggest locally generated C3 regulates the clearance of T. gondii by Macrophage through the regulation of the non-canonical IFN-γ-dependent autophagy pathway, and paint a clearer picture in the regulation of autophagy by innate immune components.

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“…Thrombosis during hemodialysis was mainly caused by excessive activation of the contact pathway of the coagulation system and platelets. 87,88 Activation of the contact pathway during hemodialysis has been demonstrated. 87,88 Numerous studies have found significant increases in FXIIa levels in the blood of patients undergoing hemodialysis.…”

Section: Mechanism Of Thrombosis In Dialysismentioning

confidence: 98%

“…Thrombosis during hemodialysis was mainly caused by excessive activation of the contact pathway of the coagulation system and platelets. 87,88…”

Section: Introductionmentioning

confidence: 99%

The Crosstalk between Nephropathy and Coagulation Disorder: Pathogenesis, Treatment, and Dilemmas

Qiu

Pang

Xiang

et al. 2023

JASN

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The interaction between the kidney and the coagulation system greatly impacts each other due to the abundant vessel distribution and blood perfusion in the kidney. Clinically, the risks of complicated thrombosis and bleeding have become important concerns in the treatment of nephropathies, especially nephrotic syndrome, chronic kidney disease, end-stage renal disease, and nephropathy patients undergoing renal replacement therapies. Adverse effects of anticoagulant or procoagulant therapies in nephropathy patients, especially anticoagulation-related nephropathy, heparin-induced thrombocytopenia, and bleeding, seriously worsen the prognosis of patients, which have become challenges for clinicians. Over the decades, the interaction between the kidney and the coagulation system has been widely studied. However, the effects of the kidney on the coagulation system have not been systematically investigated. Although some coagulation-related proteins and signaling pathways have been shown to improve coagulation abnormalities while avoiding additional kidney damage in certain kidney diseases, their potential as anticoagulation targets in nephropathy requires further investigation. Here, we review the progression of research on the crosstalk between the coagulation system and kidney diseases, and systematically analyze the significance and shortcomings of previous studies to provide new sight into future research. In addition, we highlight the status of clinical treatment for coagulation disorder and nephropathy caused by each other, indicating guidance for the formulation of therapeutic strategies or drug development.

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Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review

Cited by 15 publications

References 119 publications

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

Immune System Dysfunction and Inflammation in Hemodialysis Patients: Two Sides of the Same Coin

Locally generated C3 regulates the clearance of Toxoplasma gondii by IFN-γ-primed macrophage through regulation of xenophagy

The Crosstalk between Nephropathy and Coagulation Disorder: Pathogenesis, Treatment, and Dilemmas

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