RT Journal Article
SR Electronic
T1 Investigation of the transcriptional profile of human kidneys during machine perfusion reveals potential benefits of haemoadsorption
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 521294
DO 10.1101/521294
A1 John R. Ferdinand
A1 Sarah A. Hosgood
A1 Tom Moore
A1 Christopher J. Ward
A1 Tomas Castro-Dopico
A1 Michael L. Nicholson
A1 Menna R. Clatworthy
YR 2019
UL http://biorxiv.org/content/early/2019/01/16/521294.abstract
AB Transplantation is the optimal treatment for most patients with end stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to re-condition marginal organs but the mechanisms by which NMP might benefit transplant kidneys are not fully understood. Furthermore, the question of whether removal of pro-inflammatory mediators from the perfusate might offer additional benefits in optimising kidneys prior to transplantation has not been addressed. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global transcriptome of kidneys, and then went on to investigate the impact of adding a haemoadsorption device to the NMP circuit. We found that cold storage significantly reduced the expression of inflammatory genes, but also of genes required for energy generation such as those encoding oxidative phosphorylation (OXPHOS) enzymes. In contrast, during NMP, there was marked upregulation OXPHOS genes, as well as a number of immune and inflammatory pathway genes. The induction of inflammatory genes during NMP was substantially attenuated by the addition of a haemoadsorber to the perfusion circuit, which also further increased OXPHOS pathway gene expression. Together, our data suggest that absorption of pro-inflammatory mediators from the perfusate represents a useful intervention that may further improve organ viability and should be tested in clinical practice.Single sentence summary: The use of a haemoadsorber during machine perfusion reduces inflammatory gene expression, with potential benefits for kidney transplantation.