Systemic complement activation in deceased donors is associated with acute rejection after renal transplantation in the recipient.

BACKGROUND: Acute rejection after renal transplantation has been shown to be negatively associated with long-term graft survival. Identifying donor factors that are associated with acute rejection in the recipient could help to a better understanding of the relevant underlying processes that lead to graft injury. Complement activation has been shown to be an important mediator of renal transplant related injury. In this study, we analyzed the effect of systemic complement activation in deceased donors before transplantation of their kidneys on posttransplant outcome in the recipient. METHODS: Plasma from 232 deceased brain-dead and deceased cardiac-dead donors were analyzed for the complement activation markers C5b-9, C4d, Bb, and complement component mannan binding lectin by ELISA. The association of these parameters with posttransplant outcome in recipients was analyzed in a multivariate regression model. RESULTS: It was found that C5b-9 level in donor plasma is associated with biopsy-proven acute rejection in the recipient during the first year after renal transplantation (P = 0.035). Both in deceased brain-dead and deceased cardiac-dead donors increased complement activation was found. CONCLUSIONS: In conclusion, we found C5b-9 in the donor to be associated with acute rejection of renal transplants in the recipient. Whether targeting complement activation in the donor may ameliorate acute rejection in the recipient needs to be studied

Targeting complement activation in brain-dead donors improves renal function after transplantation.

Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient

Increased renal C5a receptor expression and systemic complement activation in brain dead donors

Nephrolog

Including species interactions in risk assessments for global change

Most ecological risk assessments for global change are restricted to the effects of trends in climate or atmospheric carbon dioxide. In order to move beyond investigation of the effects of climate alone, the CLIMAX (TM) model was extended to investigate the effects of species interactions, in the same or different trophic levels, along environmental gradients on a geographical scale. Specific needs that were revealed during the investigations include: better treatment of the effects of temporal and spatial climatic variation; elucidation of the nature of boundaries of species ranges; data to quantify the role of species traits in interspecies interactions; integrated observational, experimental, and modelling studies on mechanisms of species interactions along environmental gradients; and high-resolution global environmental datasets. Greater acknowledgement of the shared limitations of simplified models and experimental studies is also needed. Above all, use of the scientific method to understand representative species ranges is essential. This requires the use of mechanistic approaches capable of progressive enhancement