Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

Moers, Cyril; Smits, Jacqueline M.; Maathuis, Mark-Hugo J.; Treckmann, Juergen; Gelder, F Van; Napieralski, Bogdan P.; Kasterop-Kutz, Margitta van; Heide, Jaap J. Homan van der; Squifflet, Jean‐Paul; Heurn, Ernest van; Kirste, G.; Rahmel, Axel; Leuvenink, Henri G. D.; Paul, Andreas; Pirenne, Jacques; Ploeg, Rutger J.

doi:10.1056/nejmoa0802289

Cited by 956 publications

(721 citation statements)

References 26 publications

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“…11 This pioneering study created the rationale to investigate strategies for organ preservation based on machine perfusion of kidney or liver grafts. 24,25 Furthermore, it allows study of the molecular mechanisms leading to increased endothelial sensitivity to injury in the absence of shear stress, with the aim of discovery druggable targets to prevent endothelial and tissue damage during organ procurement. For this purpose, we analyzed the effects of shear stress interruption and cold storage on the hepatic endothelial phenotype and function, and developed a pharmacological strategy to maintain endothelial health in the setting of organ transplantation.…”

Section: Discussionmentioning

confidence: 99%

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

et al. 2012

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Pathophysiological alterations in the endothelial phenotype result in endothelial dysfunction. Flow cessation, occurring during organ procurement for transplantation, triggers the endothelial dysfunction characteristic of ischemia/reperfusion injury, partly due to a reduction in the expression of the vasoprotective transcription factor Kruppel-like Factor 2 (KLF2). We aimed at (1) characterizing the effects of flow cessation and cold storage on hepatic endothelial phenotype, and (2) ascertaining if the consequences of cold stasis on the hepatic endothelium can be pharmacologically modulated, improving liver graft function. Expression of KLF2 and its vasoprotective programs was determined in (i) hepatic endothelial cells (HEC) incubated under cold storage conditions with or without the KLF2-inducer simvastatin, and (ii) rat livers not cold stored or preserved in cold University of Wisconsin solution (UWS) supplemented with simvastatin or its vehicle. In addition, upon warm reperfusion hepatic vascular resistance, endothelial function, nitric oxide vasodilator pathway, apoptosis, inflammation, and liver injury were evaluated in not cold stored livers or livers preserved in cold UWS supplemented with simvastatin or vehicle. Expression of KLF2 and its vasoprotective programs decrease in HEC incubated under cold storage conditions. Cold-stored rat livers exhibit a time-dependent decrease in KLF2 and its target genes, liver injury, increased hepatic vascular resistance, and endothelial dysfunction. The addition of simvastatin to the storage solution, maintained KLF2-dependent vasoprotective programs, prevented liver damage, inflammation, and oxidative stress and improved endothelial dysfunction. Conclusion: Our results provide a rationale to evaluate the beneficial effects of a vasoprotective preservation solution on human liver procurement for transplantation. (HEPATOLOGY 2012;55:921-930)

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Section: Discussionmentioning

confidence: 99%

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

et al. 2012

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“…Moers et al have shown better 1 year graft survival and lower delayed graft function rates after machine perfusion MP in a cohort composing both DCD (n=42) and DBD kidneys (n=294) [12] and these findings were replicated in other studies [13,14]. However, Moers have stated later on that three years after transplantation machine perfusion MP had no advantage over cold storage in terms of graft survival in DCD kidney transplantation.…”

Section: Discussionmentioning

confidence: 87%

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival

Sevinc¹,

Stamp

Carter

et al. 2016

Transplantation Proceedings

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“…We assessed the effect of perfusion duration on the association between post pi-GST and DGF via stratified analysis with three duration categories (<8, [8][9][10][11][12][13][14][15][16], and >16 hours). The RR estimate for DGF with each unit increase in Log e (post pi-GST) were comparable for each category in the range of 1.3 to 1.6.…”

Section: Associations Of Perfusate Gst Pump Parameters and The Outcomentioning

confidence: 99%

Glutathione S-Transferase Iso-Enzymes in Perfusate From Pumped Kidneys Are Associated With Delayed Graft Function.

Hall

Bhangoo

Reese³

et al. 2014

Transplantation

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Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

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Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

Abstract: Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

Cited by 956 publications

References 26 publications

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival

Glutathione S-Transferase Iso-Enzymes in Perfusate From Pumped Kidneys Are Associated With Delayed Graft Function.

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