Normothermic Ex-Vivo Kidney Perfusion Restores the Genetic Profile of Marginal Kidney Grafts Subjected to Warm Ischemia
Bibliographic record
Abstract
Background Increasing evidence demonstrates the superiority of normothermic ex-vivo kidney perfusion (NEVKP) over cold storage (CS) for grafts sensitive to ischemia-reperfusion injury, including kidneys procured following donation-after-cardiac-death (DCD). To account for this improvement, we investigated whether NEVKP-preservation returns the genetic profiles of DCD grafts to that of unmanipulated naïve kidneys. Methods Kidneys from 30kg Yorkshire pigs were removed following 30 minutes of warm ischemia in a model of DCD. These grafts were then stored in either static cold histidine-tryptophan-ketoglutarate solution (CS) or subjected to pressure-controlled NEVKP for 8 hours prior to heterotopic autotransplantation. Kidney biopsies were collected on POD3 and gene expression was compared with naïve porcine kidneys utilizing the Affymetrix GeneChip® Porcine Gene 1.0 ST Array platform examining over 23,000 transcripts. Validation was performed using quantitative real-time polymerase chain reaction. Results During NEVKP storage, DCD grafts demonstrated favourable perfusion characteristics including progressive lactate clearance (0hr: 10.29 +/-0.48 mmol/L vs 8hr: 1.67+/-0.67 mmol/L, n=5, P<0.01), decreasing intra-renal resistance (0hr:1.63+/-0.20 mmHg/mL/min vs 8hr:0.41+/-0.13 mmHg/mL/min, n=5, p<0.01), and continuous urine production. Post-transplantation graft function significantly improved with NEVKP compared to CS with decreased peak serum creatinine (POD1: 4.0+/-1.15mg/dL vs POD3: 12.0+/-0.78mg/dL, n=5, p<0.01) and higher creatinine clearance on POD3 (39.6+/-11.8mL/min vs 2.6+/-0.9ml/min, n=5, p<0.01). Genomic comparison of grafts subjected to NEVKP on POD3 showed significant differences in only 27 genes when compared to naïve porcine kidneys (Table 1, >±2-fold changes in expression over naïve, n=3, P<0.05, FDR p-value<0.20). In contrast, 668 genes were significantly differentially expressed between grafts stored with CS on POD3 and naïve kidneys (Table 2, >±2-fold changes in expression over naïve, n=3, P<0.05, FDR p-value<0.20).Conclusions NEVKP restored damaged kidney grafts in a model of DCD with a genomic profile closely resembling naïve kidneys. Conversely, ongoing injury was evident in DCD grafts following CS through increased expression of genes related to inflammation, apoptosis, and repair. Together, these findings support the use of NEVKP for storage of DCD grafts that are more susceptible to ischemia-reperfusion injury.
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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) | 0.001 | 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".