Abstract
Marginal kidney graft preservation in machine perfusion (MP) is well-established. However, this method requires improvement in order to mitigate oxidative stress during ischemia-reperfusion, by using oxygenation or an O2 carrier with anti-oxidant capacities (hemoglobin of the marine worm; M101). In our preclinical porcine (pig related) model, kidneys were submitted to 1h-warm ischemia, followed by 23 h hypothermic preservation in Waves® MP before auto-transplantation. Four groups were studied: W (MP without 100%-O2), W-O2 (MP with 100%-O2; also called hyperoxia), W-M101 (MP without 100%-O2 + M101 2 g/L), W-O2 + M101 (MP with 100%-O2 + M101 2 g/L) (n = 6/group). Results: Kidneys preserved in the W-M101 group showed lower resistance, compared to our W group. During the first week post-transplantation, W-O2 and W-M101 groups showed a lower blood creatinine and better glomerular filtration rate. KIM-1 and IL-18 blood levels were lower in the W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, fractional excretion of sodium and the proteinuria/creatinuria ratio remained higher in the W group, creatininemia was lower in the W-M101 group, and kidney fibrosis was lower in M101 groups. We concluded that supplementation with M101 associated with or without 100% O2 improved the Waves® MP effect upon kidney recovery and late graft outcome.
Highlights
Kidney transplantation is the best treatment for patients with end-stage kidney disease, but the current organ shortage is a major challenge
There was a slight increase in the perfusion flow in groups with M101 supplementation (W-M101 and W-O2 + M101), compared to the groups without M101 (W and W-O2), with significant differences
We showed that M101 supplementation during ex vivo preservation perfusion improved kidney graft recovery and outcome
Summary
Kidney transplantation is the best treatment for patients with end-stage kidney disease, but the current organ shortage is a major challenge This shortage leads to increased acceptance of high risk donors, such as Donation after Circulatory Death (DCD) and expanded criteria donors (ECD). Kidneys procured from such donors are more sensitive to ischemia-reperfusion (IR), and subsequently more susceptible to tardive lesions/dysfunctions [1]. Despite the demonstrated benefits of machine perfusion (MP) in preserving DCD kidneys, the complications arising from DCD graft transplantation remain elevated [2] This MP method still requires improvement to minimize ischemia-related injuries
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