Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischaemia–reperfusion injury by mitigating renal graft apoptosis and inflammation
Bibliographic record
Abstract
UNLABELLED: What's known on the subject? and What does the study add? Hydrogen sulphide (H(2) S) has recently been classified as a member of the family of small gaseous molecules called gasotransmitters and has been found to have many important physiological functions. Several recent studies have elucidated the protective effects of H(2) S in many models of tissue ischaemia-reperfusion injury (IRI), including hepatic, myocardial, pulmonary, cerebral and renal IRI. It has previously been shown that H(2) S has a number of properties that may contribute to its protection against IRI, including vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant effects, although the specific actions appear to vary between tissues. The few studies investigating the effects of H(2) S against renal IRI have only involved clamping of the renal pedicle to induce warm IRI. This study investigated the protective effects of H(2) S in the context of renal transplantation (RTx), which generally involves a more severe period of prolonged cold IRI. A previous study investigated the actions of H(2) S in RTx, but it was performed ex vivo and did not involve actual transplantation of donor kidneys. To our knowledge, this is the first study using a clinically relevant model of RTx to show that treatment of donor kidneys with H(2) S during preservation is protective against prolonged cold IRI. These findings suggest that H(2) S has potential utility in improving clinical organ preservation techniques and increasing the overall success of organ transplantation. OBJECTIVE: • To characterize the effects of hydrogen sulphide (H(2) S), an endogenously produced molecule recently described to have protective effects against warm ischaemic tissue injury, in mitigating transplantation-associated prolonged cold ischaemia-reperfusion injury (IRI) in a clinically applicable in vivo model of renal transplantation (RTx). MATERIALS AND METHODS: • After undergoing bilateral native nephrectomy, Lewis rats underwent RTx with kidneys that were flushed with either cold (4 °C) standard University of Wisconsin preservation solution (UW) or cold UW + 150 µM NaHS (H(2) S) solution and stored for 24 h at 4 °C in the same solution. • Recipient rats were monitored for a 14-day time course using metabolic cages to assess various characteristics of renal graft function. • Renal grafts were removed at time of death or after the rats were killed for histological, immunohistochemical and quantitative PCR analysis. RESULTS: • H(2) S-treated rats exhibited immediate and significant (P < 0.05) decreases in serum creatinine levels, increased urine output and increased survival compared with UW-treated rats. • H(2) S-treated grafts showed significantly reduced glomerular and tubular necrosis and apoptosis, diminished graft neutrophil and macrophage infiltrates and a trend towards improved inflammatory and anti-apoptotic cytokine profiles. CONCLUSION: • Our results provide the first evidence that supplemental H(2) S can mitigate renal graft IRI incurred during transplantation and prolonged cold storage, improving early graft function and recipient survival in a clinically applicable model of RTx.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".