Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Pushpakumar, Sathnur; Perez-Abadia, Gustavo; Soni, Chirag; Wan, Rong; Todnem, Nathan; Patibandla, Phani K.; Fensterer, Tathyana; Zhang, Qunwei; Barker, John H.; Maldonado, Claudio

doi:10.1016/j.jss.2011.06.010

Cited by 16 publications

(10 citation statements)

References 52 publications

(46 reference statements)

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“…Delayed graft function is characterised by tubular dysfunction, interstitial inflammation, and altered microcirculation (Moore et al 2008 ; Ponticelli 2014 ). Several studies have shown that complement may be involved in the pathogenesis of DGF (Castellano et al 2016 ; Damman et al 2015 ; Pushpakumar et al 2011 ; Yu et al 2016 ). Yu et al ( 2016 ) have shown that blocking the terminal complement pathway prevented reperfusion injury and increased renal graft survival.…”

Section: Discussionmentioning

confidence: 99%

Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients

Dąbrowska-Żamojcin

Czerewaty

Malinowski

et al. 2017

Arch. Immunol. Ther. Exp.

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Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction. Among patients with DGF, we observed a significantly increased frequency of rs7851696 GT and TT genotypes as well as T allele (TT + GT vs GG OR 1.98, 95% CI 1.12–3.48, p = 0.02; T vs G OR 2.08, 95% CI 1.27–3.41, p = 0.005). There was also an increased frequency of rs4521835 GG and TG genotypes as well as G alleles; however, these differences were on the borderline of statistical significance (GG + TG vs TT, OR 1.75, 95% CI 0.98–3.12, p = 0.07; G vs T OR 1.45, 95% CI 1.00–2.09, p = 0.050). In addition, we observed an increased frequency of acute allograft rejection in carriers of ficolin-2 rs7851696 T alleles on the borderline of statistical significance (TT + GT vs GG OR 1.75, 95% CI 0.97–3.16, p = 0.08), but the frequency of T allele was significantly higher in patients with AR (T vs G OR 1.71, 95% CI 1.02–2.87, p = 0.048). The results of our study suggest that ficolin-2 rs7851696 gene polymorphism influences kidney allograft functions, with T allele increasing the risk of DGF and AR.

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Section: Discussionmentioning

confidence: 99%

Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients

Dąbrowska-Żamojcin

Czerewaty

Malinowski

et al. 2017

Arch. Immunol. Ther. Exp.

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“…It has been shown that IRI activates many signaling pathways and upregulates many genes that eventually lead to complement cascade activation and therefore cell apoptosis and death [46]. In one study, mouse kidneys were flushed with and preserved in a solution containing a cocktail small interference RNA (siRNA) targeting complement 3, RelB, and Fas expression.…”

Section: Machine Perfusion: a Platform For Organ Treatmentmentioning

confidence: 99%

Opportunities for Therapeutic Intervention During Machine Perfusion

Karimian

Yeh

2017

Curr Transpl Rep

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Purpose of review There is a vast discrepancy between the number of patients waiting for organ transplantation and the available donor organs. Ex vivo machine perfusion (MP) has emerged in an effort to expand the donor pool, by improving organ preservation, providing diagnostic information, and more recently, acting as a platform for organ improvement. This article reviews the current status of MP with a focus on its role in organ preconditioning and therapeutic interventions prior to transplantation. Recent findings MP has allowed longer organ preservation compared to conventional static cold storage and allowed the use of organs that might otherwise have been discarded. Moreover, experimental studies have investigated the role of MP in reducing ischemia reperfusion injury of lungs, kidneys and livers by applying mesenchymal stem cells (MSCs), anti-inflammatory agents, cytotopic anticoagulants, and defatting cocktails. Summary MP has opened a new era in the field of organ transplantation and tissue medication.

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“…Complement C3 expression on the donor also plays an important role in donor injury during ischaemia [8]. Complement inhibition in brain dead donors has been shown to improve graft function [9], and several targeted complement inhibition approaches are now being investigated [10 ▪ ]. …”

Section: Cellular Events Associated With Renal Ischaemic Injurymentioning

confidence: 99%

Innate immunity in donor procurement

Cheung

Kasimsetty

McKay

2013

Current Opinion in Organ Transplantation

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Purpose of review Ischaemic kidney injury occurs during organ procurement and can lead to delayed graft function or nonviable grafts. The innate immune system is a key trigger of inflammation in renal ischaemia. This review discusses the components of innate immunity known to be involved in renal ischaemic reperfusion injury (IRI). Understanding how inflammatory damage is initiated in renal IRI is important for the development of targeted therapies aimed at preserving the donor organ. Recent findings Much remains to be determined about the role of innate immune signalling in renal ischaemia/reperfusion injury. Recently, discoveries about complement receptors, Toll-like receptors (TLRs), NOD-like receptors (NLRs) and inflammasomes have opened new avenues of exploration. We are also now learning that macrophages, complement and TLR activation may have additional roles in renal repair following IRI. Summary A greater understanding of the mechanisms that contribute to innate immune-mediated renal ischaemic damage will allow for the development of therapeutics targeted to the donor organ. New data suggest that treatment limited to specific receptors on specific cells, or localized to specific regions within the kidney, may provide novel approaches to maximize our use of donor organs, particularly those that may have been discarded due to prolonged preimplantation ischaemia.

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Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Cited by 16 publications

References 52 publications

Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients

Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients

Opportunities for Therapeutic Intervention During Machine Perfusion

Innate immunity in donor procurement

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