Ogurlu, Baran (2022) Prolonged controlled oxygenated rewarming improves immediate tubular function and energetic recovery of porcine kidneys during normothermic machine perfusion Baran. thesis, Medicine.
Full text available on request.Abstract
Normothermic machine perfusion (NMP) has come to the fore as a promising tool for more objective pre-transplant viability assessment of deceased donor kidneys. Typically, NMP is performed after a period of hypothermic preservation, which exposes the kidney to an abrupt increase in temperature and intravascular pressure. The resultant induction of rewarming injury could be alleviated by a more gradual rewarming using a technique called controlled oxygenated rewarming (COR). To date, it remains unknown how gradual the rewarming during COR should be. This project aimed to investigate which rewarming rate during COR results in the best protective effect on renal rewarming injury during subsequent NMP. For this translational laboratory study, 28 viable porcine kidneys (n = 7 per group) were obtained from a slaughterhouse. After the kidneys had sustained 30 minutes of warm ischemia and 24 hours of oxygenated hypothermic machine perfusion, they were either rewarmed abruptly by directly initiating NMP, or gradually over the course of 30, 60 or 120 minutes during COR (rate of increase in kidney temperature of 4.46%, 2.20%, and 1.10% per min) before NMP was commenced., The kidneys that were rewarmed over the course of 120 minutes (COR-120) had significantly lower fractional excretion of sodium (54.81±20.85%) at the start of NMP compared to rewarming durations of 30 minutes (COR-30) (107.5±13.04%, P < 0.001) and 60 minutes (COR-60) (90.71±19.96%, P < 0.01). In line with this, COR-120 kidneys showed significantly lower fractional excretion of glucose (44.47±18.78%) when normothermic reperfusion was initiated compared with COR-30 (104.3±11.85%, P < 0.0001) and COR-60 kidneys (84.99±20.04%, P < 0.01). Although COR-120 kidneys showed superior immediate tubular function upon the start of normothermic perfusion, this difference disappeared over the course of NMP. Furthermore, energetic recovery, approximated by regeneration of tissue ATP, was significantly improved in COR-30 (20.32±8.51 μmol/g protein) and COR-120 (20.41±5.95 μmol/g protein) compared to abruptly rewarmed kidneys (14.89±5.58 μmol/g protein; P < 0.05 for both comparisons) and COR-60 (14.67±3.96 μmol/g protein; P < 0.01 for both comparisons). In conclusion, this study found that a rewarming duration of 120 minutes with a rewarming rate of 1.10% per min during COR results in superior immediate tubular function and energetic recovery during NMP, therefore it provides the best protective effect against rewarming injury.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Moers, Cyril |
| Faculty: | Medical Sciences |
| Date Deposited: | 14 Jun 2023 11:14 |
| Last Modified: | 14 Jun 2023 11:19 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3556 |
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