Cytokine absorption during human kidney perfusion reduces delayed graft function–associated inflammatory gene signature

John R. Ferdinand, Sarah A. Hosgood, Tom Moore, Ashley Ferro, Christopher J. Ward, Tomas Castro-Dopico, Michael L. Nicholson, Menna R. Clatworthy

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome. We found that cold storage led to a global reduction in gene expression, including inflammatory pathway genes and those required for energy generation processes, such as oxidative phosphorylation (OXPHOS). In contrast, during NMP, there was marked upregulation OXPHOS genes, but also of a number of immune and inflammatory pathway genes. Using biopsies from kidneys undergoing NMP that were subsequently transplanted, we found that higher inflammatory gene expression occurred in organs with prolonged delayed graft function (DGF). Therefore, we used a hemoadsorber (HA) to remove pro-inflammatory cytokines. This attenuated inflammatory gene expression increased OXPHOS pathway genes and had potentially clinically important effects in reducing the expression of a DGF-associated gene signature. Together, our data suggest that adsorption of pro-inflammatory mediators from the perfusate represents a potential intervention which may improve organ viability.

Original languageEnglish
Pages (from-to)2188-2199
Number of pages12
JournalAmerican Journal of Transplantation
Volume21
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • clinical research / practice
  • delayed graft function (DGF)
  • donors and donation: deceased
  • kidney (allograft) function / dysfunction
  • kidney disease: immune / inflammatory
  • kidney transplantation / nephrology
  • organ perfusion and preservation
  • translational research / science

Fingerprint

Dive into the research topics of 'Cytokine absorption during human kidney perfusion reduces delayed graft function–associated inflammatory gene signature'. Together they form a unique fingerprint.

Cite this