Normothermic Ex Vivo Kidney Perfusion Preserves ATP Generation and Graft Function After Warm Ischemia, Which Is Further Enhanced With Pharmacologic Mitochondrial Protection
Bibliographic record
Abstract
Background: Normothermic Ex-vivo kidney machine perfusion (NEVKP) is a novel preservation technique. We recently determined that NEVKP preserves the expression of proteins involved in mitochondrial biogenesis in kidneys. We hypothesize that ex vivo machine perfusion will replenish energy levels in mitochondria, thereby restoring mitochondrial function and reducing injury in kidney grafts. AP39, a mitochondriatargeted hydrogen sulfide donor, has been shown to stimulate mitochondrial electron transport and improve cellular bioenergetic function. Here, we investigated whether administering AP39 during NEVKP protects mitochondrial function and protects renal grafts from ischemia reperfusion injury. Methods: Porcine kidneys were subjected to either 0 or 60 minutes of warm ischemia (WI) followed by 5 hours of static cold storage (SCS) or NEVKP. The warm ischemia grafts were subsequently divided into three groups: SCS group, NEVKP group, and a group in which AP39 was additionally administered during NEVKP (NEVKP + AP39) (Fig. 2.). After contralateral nephrectomy, grafts were auto-transplanted and animals were followed for 3 days. Renal function and ATP levels were assessed. Results: All animals (n=5-6 in each group) survived the follow-up period. Grafts preserved with NEVKP had lower serum creatinine (SrCr) on postoperative day 3 compared to the SCS group (Fig. 1). Treatment with NEVKP + AP39 further reduced SrCr when compared to the NEVKP group (HB vs SCS vs NEVKP vs NEVKP + AP39: 1.7±0.3 vs 12.7±1.1 vs 7.6±2.8 vs 3.5±1.1 mg/dl, mean±SD). We measured ATP in biopsyderived cell suspensions from grafts stored using SCS, NEVKP, and NEVKP + AP39. ATP levels were increased in the NEVKP group compared with SCS group at the time of pre-implantation and this level was further increased when AP39 was administered. (SCS vs NEVKP vs NEVKP + AP39: 21.9±11.4 vs 73.6±9.3 vs 121.6±36.3 nM/10000cells). Conclusions: For grafts subjected to warm ischemia, NEVKP has the potential to preserve ATP generation and graft function, which is further enhanced with mitochondriatargeted hydrogen sulfide donor, AP39.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".