Experimental and clinical transplantation of organs from donors after uncontrolled circulatory arrest (uDCD)

Background: We present a model of extended uncontrolled DCD (uDCD), allowing sufficient time for the consent procedure in most countries.

A novel reconditioning technique allows successful transplantation after prolonged warm ischemia of kidneys from uDCD donors, using thrombolytic treatment and ex-vivo perfusion.

Plan: We will conduct a first-in-man, proof of concept study in 8 patients, using the novel model to utilize uDCD donors after extended warm ischemia time. Primary endpoint will be safety, secondary endpoint delayed graft function (DGF).

The hypothesis behind the ischemia-reperfusion injury (I/R-I) will be verified in human kidneys, and vascular endothelia function, measured with organ-bath technology and digitalPCR to genes upregulated in (I/R-I).

The method will be extended to livers subjected to uDCD ischemic trauma in pigs, with the aim to establish a clinically applicable model during the grant period.Impact:  We anticipate a positive outcome, based on extensive work in uDCD kidneys, with potential to eradicated waiting lists, reduce mortality and offer kidney transplantations to more patients in total.

This will be accomplished to a reduced cost for the healthcare system.

Furthermore, we are optimistic that the method is transferable to livers as well, which may result in the possibility to offer liver transplantation, with prolonged survival and increased quality of life as result, to new indications such as colorectal carcinomas with liver metastases.