Dataset Information

Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost.

ABSTRACT:

Background

Over 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic machine perfusion to identify transplantable livers among those currently discarded.

Study design

A series of 21 discarded human livers underwent viability assessment during normothermic machine perfusion. Cross-sectional analysis of the Scientific Registry of Transplant Recipients database and cost analysis was performed to extrapolate the case series to national experience.

Results

21 discarded human livers were included in the perfusion cohort. 11 of 20 (55%) eligible grafts met viability criteria for transplantation. Grafts in the perfusion cohort had a similar donor risk index compared with discarded grafts (n = 1402) outside of New England in 2017 and 2018 (median [IQR]: 2.0 [1.5, 2.4] vs. 2.0 [1.7, 2.3], P = .40). 705 (IQR 677-741) livers were discarded annually in the United States since 2005, translating to the potential for 398 additional transplants nationally. The median cost to identify a transplantable graft with machine perfusion was $28,099 USD.

Conclusions

Normothermic machine perfusion of discarded livers could identify a significant number of transplantable grafts, significantly improving access to liver transplantation.

SUBMITTER: Raigani S

PROVIDER: S-EPMC7944462 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost.

Raigani Siavash S De Vries Reinier J RJ Carroll Cailah C Chen Ya-Wen YW Chang David C DC Shroff Stuti G SG Uygun Korkut K Yeh Heidi H

Clinical transplantation 20200923 11

<h4>Background</h4>Over 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic machine perfusion to identify transplantable livers among those currently discarded.<h4>Study design</h4>A series of 21 discarded human livers underwent viability assessment during normothermic machine perfusion. Cross-sectional analysis of the Scientific Registry of Transplant Recipients databa ...[more]

PMID: 32860634

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Project description:Background The gap between demand and supply of kidneys for transplantation necessitates the use of kidneys from extended criteria donors. Transplantation of these donor kidneys is associated with inferior results, reflected by an increased risk of delayed graft function. Inferior results might be explained by the higher immunogenicity of extended criteria donor kidneys. Normothermic machine perfusion (NMP) could be used as a platform to assess the quality and function of donor kidneys. In addition, it could be useful to evaluate and possibly alter the immunological response of donor kidneys. In this study, we first evaluated whether complement was activated during NMP of porcine and human discarded kidneys. Second, we examined the relationship between complement activation and pro-inflammatory cytokines during NMP. Third, we assessed the effect of complement activation on renal function and injury during NMP of porcine kidneys. Lastly, we examined local complement C3d deposition in human renal biopsies after NMP. Methods NMP with a blood-based perfusion was performed with both porcine and discarded human kidneys for 4 and 6 h, respectively. Perfusate samples were taken every hour to assess complement activation, pro-inflammatory cytokines and renal function. Biopsies were taken to assess histological injury and complement deposition. Results Complement activation products C3a, C3d, and soluble C5b-9 (sC5b-9) were found in perfusate samples taken during NMP of both porcine and human kidneys. In addition, complement perfusate levels positively correlated with the cytokine perfusate levels of IL-6, IL-8, and TNF during NMP of porcine kidneys. Porcine kidneys with high sC5b-9 perfusate levels had significantly lower creatinine clearance after 4 h of NMP. In line with these findings, high complement perfusate levels were seen during NMP of human discarded kidneys. In addition, kidneys retrieved from brain-dead donors had significantly higher complement perfusate levels during NMP than kidneys retrieved from donors after circulatory death. Conclusion Normothermic kidney machine perfusion induces complement activation in porcine and human kidneys, which is associated with the release of pro-inflammatory cytokines and in porcine kidneys with lower creatinine clearance. Complement inhibition during NMP might be a promising strategy to reduce renal graft injury and improve graft function prior to transplantation.

Dataset Information

Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost.

Background

Study design

Results

Conclusions

Publications

Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost.

Similar Datasets

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