Clinical and genetic epidemiology of renal transplantation
Systems Biology of Acute Renal Allograft Failure (ARF)
FWF – P15672, P18325, P21436 and P25196, EU FP7-PEOPLE-2012-IOF (grantt# 328613)
Aim of this long term research avenue is to elucidate the molecular mechanisms of postischemic allograft injury and delayed graft function. Most of this work was funded by the FWF. Over the last years we found that inflammation in the donor organ was highly predictive of DGF. The proof of concept whether the inflammation is causally related to DGF was undertaken in a large blinded RCT of over 300 deceased donors where steroids were administered to the dead organ donor before the organs were harvested. Genomics of kidney tissue was performed at the end of the cold ischemic time to check whether randomization dosing and timing was correct. The main outcome was the rate of DGF and graft patency.
Inflammation in the donor organ could be suppressed by this intervention but the clinical outcome of DGF incidence did not change, suggesting other responsible drivers of ARF (e.g. Kainz A, Wilflingseder J, Mitterbauer C, Haller M, Burghuber C, Perco P, Langer RM, Heinze G, Oberbauer R. Steroid Pretreatment of Organ Donors to Prevent Postischemic Renal Allograft Failure. A Randomized, Controlled Trial. Ann Int Med 2010; 153:222-230).
Given the extraordinary importance of ARF as main risk factor for impaired graft survival, we recently started to investigate whether post transcriptional regulation of ARF and rejection were influenced by specific miRNAs. Further research in this very area will be conducted in the recently funded EU-FP7-2012 project “AnatgomiR as novel treatment of postischemic acute renal allograft failure” (RO coordinator, grant# 328613).