scholarly journals The Role of the Complement System in Acute Kidney Injury

2013 ◽  
Vol 33 (6) ◽  
pp. 543-556 ◽  
Author(s):  
James W. McCullough ◽  
Brandon Renner ◽  
Joshua M. Thurman
Keyword(s):  
Acute Kidney Injury ◽  
Complement System ◽  
Kidney Injury ◽  
The Complement System

scholarly journals Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage

2020 ◽  
Vol 11 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Giovanni Stallone ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Complement System ◽  
Kidney Diseases ◽  
Critical Role ◽  
Graft Function ◽  
Kidney Injury ◽  
Increased Risk ◽  
Wide Range ◽  
Renal Aging

The aberrant activation of complement system in several kidney diseases suggests that this pillar of innate immunity has a critical role in the pathophysiology of renal damage of different etiologies. A growing body of experimental evidence indicates that complement activation contributes to the pathogenesis of acute kidney injury (AKI) such as delayed graft function (DGF) in transplant patients. AKI is characterized by the rapid loss of the kidney’s excretory function and is a complex syndrome currently lacking a specific medical treatment to arrest or attenuate progression in chronic kidney disease (CKD). Recent evidence suggests that independently from the initial trigger (i.e., sepsis or ischemia/reperfusions injury), an episode of AKI is strongly associated with an increased risk of subsequent CKD. The AKI-to-CKD transition may involve a wide range of mechanisms including scar-forming myofibroblasts generated from different sources, microvascular rarefaction, mitochondrial dysfunction, or cell cycle arrest by the involvement of epigenetic, gene, and protein alterations leading to common final signaling pathways [i.e., transforming growth factor beta (TGF-β), p16ink4a, Wnt/β-catenin pathway] involved in renal aging. Research in recent years has revealed that several stressors or complications such as rejection after renal transplantation can lead to accelerated renal aging with detrimental effects with the establishment of chronic proinflammatory cellular phenotypes within the kidney. Despite a greater understanding of these mechanisms, the role of complement system in the context of the AKI-to-CKD transition and renal inflammaging is still poorly explored. The purpose of this review is to summarize recent findings describing the role of complement in AKI-to-CKD transition. We will also address how and when complement inhibitors might be used to prevent AKI and CKD progression, therefore improving graft function.

scholarly journals A look at the C3 and C5 proteins in the Covid-19

2021 ◽  
Vol 43 (115) ◽  
pp. 1-9
Author(s):  
Henry David Mosquera-Daza
Keyword(s):  
Immune Responses ◽  
Complement System ◽  
Biological Activities ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
First Line ◽  
Global Pandemic ◽  
Acute Injuries ◽  
The Complement System

The emergency caused by the new SARS-CoV-2 virus, which causes the Covid-19 disease, has triggered a global pandemic. One of the most characteristic factors of SARS-CoV-2 virus infection is the deregulated activation of the complement system, especially by proteins C3 and C5. These proteins trigger initiation reactions such as maintenance of inappropriate biological activities in addition to uncontrolled immune responses by immune cells, especially neutrophils. They generate various pathologies such as acute stroke, heart attack, coagulopathies, multiorgan failure, inflammation, immunothrombinosis, heart failure, acute kidney injury, acute injuries in the lung area, thrombotic microangiopathy, pneumonia, and dysfunctional immune responses. Because of the crucial role played by proteins C3 and C5 in the infection by the SARS-COV-2 virus, new complement system inhibition treatments have emerged as a possible first line of defense against the worst symptoms developed during Covid-19 disease. This article will review in a general way, the role of C3 and C5 proteins and the treatments aimed at the inhibition of these same proteins during SARS-CoV-2 infection.

Exogenous biological renal support improves kidney function in rhabdomyolysis-induced acute kidney injury in mice

2021 ◽  
Author(s):  
Chao Liu ◽  
Kun Chi ◽  
Xiaodong Geng ◽  
Quan Hong ◽  
Zhi Mao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Complement System ◽  
Bioinformatics Analysis ◽  
Kidney Injury ◽  
Functional Enrichment ◽  
Muscle Fibres ◽  
Recipient Mouse ◽  
The Complement System ◽  
Renal Support

Abstract BackgroundRhabdomyolysis (RM) is a clinical syndrome characterised by the breakdown of skeletal muscle fibres and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous study, exogenous biological renal support alleviates renal ischaemia-reperfusion injury (IRI) in elderly mice. This study aimed to determine whether exogenous biological renal support promoted renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved.MethodsA parabiosis animal model was established to investigate effects of exogenous biological renal support on RM-induced AKI. Male wild-type C57BL/6 mice and C57BL/6-TgN (ACTb-EGFP) transgenic mice were used to determine whether shared circulation was established among parabiotic pairs 3 weeks after parabiosis surgery. Mice were divided into three groups: the control group (sterile saline injected); RM group (glycerol (8 mL/kg) injected); and parabiosis + RM group (three weeks after the parabiosis model was established, the recipient mouse was injected with glycerol). Blood samples and kidney tissue were collected for further processing 48 hours after RM induction. Bioinformatics analysis was conducted with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, functional enrichment analysis and clustering analysis.ResultsAt 48 hours after the procedure, all mice survived. Exogenous biological renal support attenuated the histological and functional deterioration in RM-induced AKI in mice. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated kidney injury through multiple pathways, including suppressing the complement system; attenuating oxidative stress, inflammation, and apoptosis; and increasing proliferation.ConclusionsExogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and apoptosis; and promoting tubular cell proliferation. Our study provides new ideas for effectively preventing and treating RM-induced AKI and provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.

scholarly journals Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Liu ◽  
Kun Chi ◽  
Xiaodong Geng ◽  
Quan Hong ◽  
Zhi Mao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cell Death ◽  
Complement System ◽  
Bioinformatics Analysis ◽  
Kidney Injury ◽  
Functional Enrichment ◽  
Control Group ◽  
The Complement System ◽  
Renal Support

Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia–reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved.Methods: A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis.Results: No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation.Conclusions: Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.

scholarly journals Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

scholarly journals A zebrafish model of infection-associated acute kidney injury

2018 ◽  
Vol 315 (2) ◽  
pp. F291-F299 ◽  
Author(s):  
Xiaoyan Wen ◽  
Liyan Cui ◽  
Seth Morrisroe ◽  
Donald Maberry ◽  
David Emlet ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Unmet Need ◽  
Kidney Injury ◽  
Edwardsiella Tarda ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Pericardial Edema ◽  
Kidney Injury Molecule 1 ◽  
Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

The role of the complement system in hereditary angioedema

2017 ◽  
Vol 89 ◽  
pp. 59-68 ◽  
Author(s):  
Dorottya Csuka ◽  
Nóra Veszeli ◽  
Lilian Varga ◽  
Zoltán Prohászka ◽  
Henriette Farkas
Keyword(s):  
Complement System ◽  
Hereditary Angioedema ◽  
The Complement System
Sign in / Sign up

Export Citation Format

Share Document