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.

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.