Kidney transplantation remains the ultimate treatment option for patients with end-stage renal disease. However, the global shortage in donor kidneys, exacerbated by challenges such as ischemia–reperfusion injury (IRI), reduces renal graft viability and negatively impacts post-transplant outcomes. Static cold storage, the gold standard of organ preservation, reduces metabolic demand but increases the risk of cold-induced mitochondrial dysfunction and IRI, especially in marginal kidneys. The introduction of machine perfusion techniques allows renal grafts and other solid organ grafts to be preserved at a wider range of temperatures. Organ preservation temperatures play an important role in determining post-transplant outcomes in the transplantation of the kidney and other transplantable solid organs. Therefore, determining the optimal preservation temperature may help increase organ utilization by avoiding unnecessary graft discards and increasing the safe use of marginal organs. This review discusses the impact of various preservation temperatures and methods of preservation on post-transplant outcomes in renal grafts and other organ grafts. Drawing from preclinical, clinical, and meta-analytic studies, we compare hypothermic (0–4 °C), moderate hypothermic (10 °C), subnormothermic (20–32 °C), normothermic (35–37 °C), and subzero preservation strategies, and cellular and molecular changes that occur in renal grafts and other solid organ grafts during preservation at these temperatures. Overall, temperature-controlled machine perfusion outperforms static preservation of renal grafts and other solid organ grafts from marginal and deceased donors, potentially expanding donor pools and improving long-term graft survival, and suggests the need for future research to determine optimal preservation temperature for renal grafts and other solid organ grafts to improve viability and post-transplant outcomes.

Background: Frostbite injury is a thermal injury where ice crystals form in skin tissues and subsequently lead to damage due to prolonged exposure to cold temperatures below 0 °C. The extremities are mostly affected, leading to potential amputation. As there is no pharmacological treatment of frostbite injury, we recently reported that non-clinically viable hydrogen sulfide (H₂S) donors promote frostbite wound healing in mice. In this study, we investigated whether commonly used cosmetic creams supplemented with sodium thiosulfate (STS), a clinically viable H₂S donor drug, also promote healing of frostbite wounds. Methods: Frozen magnets (−80 °C) were placed on the dorsal skin of 40 C57BL/6 mice for 3 min to induce frostbite injury. Next, commercially available cosmetic creams (Aveeno, Dove, Neutrogena, and Nivea) were topically applied on frostbite wounds daily for 14 days with or without 150 µM of STS supplementation. The mice were sacrificed on day 15 after induction of frostbite injury, and samples of the injured dorsal skin tissue were collected for analysis. Results: Addition of STS enhanced frostbite wound healing, as evidenced by progressive and significantly reduced wound area by about 50% and inflammation (p < 0.05), and markedly increased granulation tissue formation by >45%, fibroblast maturation by >28%, and re-epithelialization by >63% compared to control groups (p < 0.05), with Nivea producing a superior wound-healing effect. Also, STS supplementation significantly upregulated the expression of CD31 (by >25%), KI-67 (by >25%), CD163 (by >20%), fibronectin (by >14%), and cytokeratin (by >50%) in frostbite wounds compared to control groups, with Aveeno and Nivea producing a better wound-healing effect than Dove and Neutrogena creams. Conclusions: In conclusion, STS accelerated healing of frostbite wounds. Therefore, it could be considered as a novel pharmacological treatment of clinical frostbite.

Chronic kidney disease (CKD) affects over 10% of the global population, with end-stage renal disease (ESRD) necessitating renal replacement therapy. Kidney transplantation remains the optimal treatment for ESRD. However, the global donor kidney shortage crisis has led to increased reliance on deceased donor kidneys. Donors are classified as either donation after brain death (DBD) or donation after circulatory death (DCD), each associated with distinct ischemic injuries that impact graft function. Ischemia–reperfusion injury (IRI) plays a pivotal role in transplant outcomes, triggering oxidative stress, inflammation, and endothelial dysfunction. While static cold storage (SCS) remains the gold standard for organ preservation, alternative strategies such as hypothermic or normothermic machine perfusion (HMP and NMP), use of oxygen carriers during storage, and supplemental compounds to storage solutions have emerged, offering potential benefits in preserving graft viability. This review explores the cellular and molecular mechanisms of ischemic injury in deceased donor kidneys, preservation strategies tested in preclinical models, and emerging therapeutic interventions aimed at improving adverse post-transplant outcomes.

Despite their reduced viability, kidneys from donors-after-circulatory-death (DCD) increase the pool of transplantable kidneys. Molecular hydrogen (H₂) is emerging as a gas with therapeutic potential against graft injury. We investigated the effect of H₂ in an ex vivo porcine model of DCD kidney transplantation. Renal arteries of male Yorkshire pigs (n = 6) were clamped in situ for 60 min to induce ischemia, and ureters and arteries were cannulated to mimic DCD kidney injury. Upon nephrectomy, kidneys were flushed with UW solution or H₂-saturated UW solution and then preserved by machine perfusion at 4 °C for 4 h followed by a 4-h reperfusion period with warm autologous blood. Urine and arterial blood samples were collected hourly. H₂ preserved renal architecture, evidenced by significantly reduced tubular necrosis and renal expression of damage markers, which corresponded with the downregulated renal expression of pro-inflammatory genes compared to the UW-only group (p < 0.05). H₂ also markedly reduced levels of serum creatinine, BUN and intrarenal resistance, while flow rate, creatinine clearance and urine output were significantly higher, which positively correlated with Trx-1 and HO-1 expression in comparison with UW only group (p < 0.05). Improvement in renal graft quality and function is associated with Trx-1/HO-1 activation, suggesting preliminary clinical trials in kidney transplantation.

Background: Subnormothermic oxygenated machine perfusion has been shown to improve kidney preservation in the preclinical setting. However, whether oxygenated perfusion without an oxygen carrier provides superior protection over standard hypothermic machine perfusion at 4 °C in human kidneys has not been established. Methods: In this study, we assessed whether oxygenated University of Wisconsin (UW) solution perfusion at 22 °C provides improved protection compared with conventional hypothermic machine perfusion (HMP) at 4 °C using a paired human kidney model. Five pairs of discarded human kidneys were recruited for the study. For each donor pair, one kidney was randomized to 12 h oxygenated UW perfusion at 22 °C and the contralateral kidney was perfused at 4 °C with a clinically relevant kidney perfusion pump. After preservation, both kidneys were reperfused with whole blood at 37 °C for 4 h. Hemodynamic and functional parameters were assessed during preservation and reperfusion, including vascular resistance, renal blood flow, creatinine clearance, blood urea nitrogen, electrolyte levels, tissue oxygenation, and urine output. Histological injury was evaluated and a panel of kidney injury biomarkers were also measured. Results: Vascular resistance during the preservation period was significantly lower in the kidneys preserved at 22 °C compared to the HMP group, indicating improved flow dynamics. However, the improved vascular resistance observed during 22 °C preservation did not translate into superior post-reperfusion kidney function or tissue protection compared with 4 °C HMP. Renal blood flow, creatinine clearance, tissue oxygenation, cytochrome c release and malondialdehyde (MDA) levels were comparable between groups, while kidneys preserved at 22 °C had significantly higher acute tubular necrosis scores, higher blood urea nitrogen (BUN) levels, increased calbindin, glutathione S-transferase A1, monocyte chemoattractant protein-1 levels, and lower epidermal growth factor levels. Conclusion: These data demonstrate that oxygenated UW perfusion at 22 °C fails to provide superior protection to conventional HMP at 4 °C in discarded human kidneys transplantation model.