A novel strategy for preserving renal grafts in an ex vivo setting: potential for enhancing the marginal donor pool.
Renal transplantation remains the best treatment option for patients with end-stage renal failure. However, the shortage of renal grafts remains a big challenge. Renal graft ischemic injuries that occur before and after graft retrieval have a devastating effect on graft survival, especially on grafts from marginal donors. This study was conducted to assess the protective effect against ischemic injury of a preservative solution supplemented with xenon (Xe), when used on ex vivo kidney grafts in a rat renal transplant model, and to explore the underlying mechanisms in vitro. Lewis rat renal grafts were stored in Soltran preservative solution at 4°C, saturated with nitrogen (N2) or Xe gas (70% Xe or N2, with 5% CO2 balanced with O2) for 24 or 48 h. Grafts stored in Xe-saturated preservative solution demonstrated significantly less severe histopathologic changes, together with enhanced B-cell lymphoma (Bcl)-2 and heat shock protein (HSP)-70 expression. After engraftment in the Lewis rat recipient, renal function was significantly improved in the Xe-treated grafts, and macrophage infiltration and fibrosis were reduced. Xe exposure enhanced Bcl-2 and HSP-70 expression in human renal tubular epithelial (HK-2) cells and prevented mitochondrial and nuclear damage. The release of the apoptogenic factors cytochrome c, apoptosis-inducing factor (AIF), and proinflammatory high-mobility group protein B1 (HMGB-1) was effectively suppressed. This study thus demonstrated for the first time that Xe confers renoprotection on renal grafts ex vivo and is likely to stabilize cellular structure during ischemic insult. The current study has significant clinical implications, in which the use of Xe ex vivo could enhance the marginal donor pool of renal grafts by preventing graft loss due to ischemia.
1D.M., Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Rd., London SW10 9NH, UK. d.ma@imperial.ac.uk.
Hailin
H
Zhao
Jiaolin
J
Ning
Sinead
S
Savage
Heechan
H
Kang
Kaizhi
K
Lu
Xia
X
Zheng
Andrew J T
AJ
George
Daqing
D
Ma
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation; D009926:Organ Preservation / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014978:Xenon / Q000494:pharmacology*
D051033:Apoptosis Inducing Factor; D018840:HSP70 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014978:Xenon; D045304:Cytochromes c
ischemic injury; organ preservation; organ transplantation; renoprotection; xenon