Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation

Damman, Jeffrey; Nijboer, Willemijn N.; Schuurs, Theo A.; Leuvenink, Henri G. D.; Morariu, Aurora M.; Tullius, Stefan G.; Goor, Harry van; Ploeg, Rutger J.; Seelen, Marc A.

doi:10.1093/ndt/gfq717

Cited by 101 publications

(108 citation statements)

References 54 publications

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“…This finding is in accordance with results of previous experimental studies, in which changes in renal C3 gene expression were examined during reperfusion in mice subjected to renal transplantation (18). The study by Damman et al (18) showed that the most pronounced local renal activation of the CC occurs during brain death in experimental animals and that the CC remains at the same high level during the transplantation procedure.…”

Section: Discussionsupporting

confidence: 90%

Clinical Analysis of Perioperative Complement Activity during Ischemia/Reperfusion Injury following Renal Transplantation

Błogowski

Dołęgowska²,

Sałata³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The complement cascade seems to be an important mediator modulating renal ischemia/reperfusion injury. This study analyzed whether significant changes occur in the levels of a terminal panel of complement molecules (C3a, C5a, and C5b-9/membrane attack complex) during the early phase of human kidney allograft reperfusion and evaluated the potential association of these changes with clinical post-transplant graft function in kidney transplant recipients.Design, setting, participants, & measurements Seventy-five renal transplant recipients undergoing transplantation between 2004 and 2006 were enrolled in the study and divided into early, slow, and delayed graft function groups. Blood samples were collected perioperatively during consecutive minutes of allograft reperfusion from the renal vein. Levels of complement molecules were measured using ELISA.Results Analysis revealed no significant changes in C3a and C5a levels throughout reperfusion. The main complement molecule that was significantly associated with post-transplant graft function was C5b-9/membrane attack complex; throughout the reperfusion period, perioperative levels of C5b-9/membrane attack complex were around two to three times higher in delayed graft function patients than early and slow graft function individuals (P,0.005). In addition, C5b-9/membrane attack complex levels had a relatively high clinical sensitivity and specificity (70%-87.5%) for the prediction of early and long-term (1 year) posttransplant allograft function.Conclusions This clinical study supports a role for the complement cascade in delayed graft function development. However, additional studies are needed to elucidate the exact mechanisms responsible for this phenomenon. In addition, perioperative measurements of C5b-9/membrane attack complex are highlighted as promising potential clinical markers of post-transplant renal allograft function.

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Section: Discussionsupporting

confidence: 90%

Clinical Analysis of Perioperative Complement Activity during Ischemia/Reperfusion Injury following Renal Transplantation

Błogowski

Dołęgowska²,

Sałata³

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…Similar results were reported in human macrophages, in which C3 secretion was found to be triggered by application of C3a, an effect that was enhanced by co-administering oxidized LDL (74). Other pathways for control of C3 expression and secretion have been reported, including cytokine signaling (75)(76)(77). It will be of interest to examine the potential synergistic effects of CSE and cytokine stimulation.…”

Section: Discussionsupporting

confidence: 77%

Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation

Kunchithapautham¹,

Atkinson

Rohrer

2014

Journal of Biological Chemistry

140

120

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Background: Smoke components can generate 1) oxidative stress; 2) complement activation; 3) endoplasmic reticulum stress; and 4) lipid dysregulation. Results: In smoke-exposed RPE cells all four measures were activated, and reversed by antioxidants and blocking alternative complement pathway signaling. Conclusion: Oxidative stress and complement act synergistically in age-related macular degeneration (AMD) pathogenesis. Significance: Identifying mechanisms of lipid deposition will aid to develop new therapeutic approaches for AMD.

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“…The predictive value of the expression of complement components in preimplantation biopsies was as well investigated. Damman et al (17) acquired kidney biopsies from brain-dead donors and human living donors at the time of donation, after cold preservation, and after reperfusion of the graft. In brain-dead donors, C3 and fibrinogen deposition was increased at donation in comparison to living donors with no further deposition after cold ischemia or reperfusion.…”

Section: Tissue Biomarkersmentioning

confidence: 99%

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

Salvadori¹,

Tsalouchos²

2017

J Renal Inj Prev

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New findings in "omics" and genomics allowed us to find out new robust biomarkers that may allow a diagnosis avoiding invasive and dangerous procedures. This could be of particular importance if applied on transplant clinical practice. In kidney transplantation several pre-transplant biomarkers revealed useful either for a better renal allocation and as predictive of future outcomes as delayed graft function, rejections and long term outcome. Different biomarkers have been recently described bringing interesting results regarding predictive outcomes in the field of kidney transplantation. In this setting, an evaluation for pre-transplant biomarkers especially in the era of expanded criteria donors (ECDs) and non-heart-beating donors (NHBDs) could help transplant physicians to make decisions on allocation or even on discharge of the allograft. Furthermore, identify pre-transplant biomarkers is useful for a risk stratification of delayed graft function (DGF), acute rejection (AR) episodes and chronic allograft dysfunction (CAD) after kidney transplantation (KT). In this review, we report recent findings on pre-transplant biomarkers from various biological samples from donors or recipients. Please cite this paper as:

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Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation

Abstract: In conclusion, BD induces renal C3 and FBG expression. Moreover, C3 expression is associated with a worse allograft function early after transplantation. Therefore, targeting renal APPs in brain-dead donors, especially complement C3, may improve transplant outcome.

Cited by 101 publications

References 54 publications

Clinical Analysis of Perioperative Complement Activity during Ischemia/Reperfusion Injury following Renal Transplantation

Clinical Analysis of Perioperative Complement Activity during Ischemia/Reperfusion Injury following Renal Transplantation

Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

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