Background.: Delayed graft function (DGF) in deceased-donor kidney transplantation increases morbidity, prolongs hospitalization, and increases healthcare costs. Hypothermic machine perfusion (HMP) has emerged as a promising strategy to reduce DGF; however, large-scale real-world data remain limited. Methods.: We performed a retrospective cohort analysis using the Scientific Registry of Transplant Recipients (2014–2024), including adult dialysis-dependent recipients of deceased-donor kidneys preserved using either static cold storage (SCS) or HMP. The primary outcome was DGF, defined as dialysis requirement within 7 d posttransplant. A matched-pairs analysis was conducted using kidneys from the same donor. Results.: The overall cohort included 59 859 recipients (46.8% SCS, 53.2% HMP), with 2208 matched pairs identified. In the overall cohort, HMP grafts had longer cold ischemia times and a higher kidney donor risk index. They were more frequently obtained from older and donation after circulatory death donors. Although the overall DGF incidence was higher with HMP (34.4% versus 30.9%, P < 0.001), matched-pairs analysis revealed significantly lower DGF rates with HMP (29.8% versus 36.1%, P < 0.001). Adjusted analyses identified HMP as protective against DGF (overall cohort odds ratio, 0.71; 95% confidence interval, 0.66-0.78; paired cohort OR, 0.68; 95% CI, 0.50-0.93). Additional modifiable risk factors include prolonged cold ischemia time, higher recipient body mass index, and longer dialysis duration. Conclusions.: This real-world study demonstrates that HMP is associated with a significant reduction in DGF risk in kidney transplantation compared with SCS, supporting its broader implementation and targeted management of modifiable risk factors.

Despite improvements in kidney transplantation rates, the shortage of donor kidneys remains a critical issue, exacerbated by non-utilization of recovered kidneys due to quality concerns, necessitating advancements in perfusion methods to enhance graft outcomes and usage. Although static cold storage remains the default standard for kidney preservation, newer methods like hypothermic machine perfusion have shown improved outcomes, including reduced delayed graft function and better survival rates. Hypothermic oxygenated machine perfusion and normothermic machine perfusion offer some potential clinical benefits but studies to date have demonstrated mixed results. In the United States, LifePort and the XVIVO’s Kidney Assist Transport are the most popular hypothermic perfusion devices, with NMP devices mostly in trials. Combining perfusion with biomarkers such as mitochondrial flavin mononucleotide, neutrophil gelatinase-associated lipocalin, and osteopontin shows promise in assessing kidney viability and predicting post-transplant outcomes, though further research is also needed. Emphasis on repair biomarkers, such as uromodulin and osteopontin, aims to better predict graft outcomes and develop new therapies. While notable advancements have been made in the use of machine perfusion and viability testing for liver transplantation, additional research with larger sample sizes is essential to substantiate these results and enhance kidney transplantation outcomes.

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