Background
Kidney transplantation remains the preferred treatment for many patients with end-stage kidney disease, offering better survival and quality of life than long-term dialysis. However, the success of transplantation depends heavily on the condition of the donor kidney and the amount of ischemic injury it experiences before implantation. This is especially relevant in donation after circulatory death (DCD), where kidneys are recovered after the donor’s heart has stopped. In DCD transplantation, a period of warm ischemia occurs before the organ can be cooled and preserved, and that injury can increase the risk of delayed graft function and, in some cases, long-term graft failure.
Normothermic regional perfusion (NRP) has emerged as a strategy to reduce this injury. In NRP, circulation is restored to the abdominal organs after circulatory death using extracorporeal support, while preserving ethical and legal boundaries regarding death determination. The goal is to improve organ quality by restoring oxygen delivery before procurement. Although NRP has been increasingly adopted, questions remain about how much it improves outcomes, whether a longer NRP period is better, and which patients benefit the most.
Study Objective
This nationwide study evaluated the short- and mid-term effects of NRP in adult primary kidney transplants from DCD donors in the United States. The investigators also examined whether the duration of NRP influenced outcomes and whether certain donor or recipient subgroups gained more benefit from NRP than others.
Methods
Using United Network for Organ Sharing Standard Transplant Analysis and Research files, the researchers identified 21,010 primary adult DCD kidney transplant cases performed between 2020 and 2025. The cases were grouped according to the interval from circulatory death to aortic cross-clamp. Based on prior literature, transplants were classified as non-NRP when this interval was 0 to 30 minutes and as NRP when it was 30 to 180 minutes.
Because donor and recipient characteristics can differ significantly between groups, the study used propensity score matching to reduce confounding and create more balanced comparisons. The main outcomes were delayed graft function, length of hospital stay, graft survival, and patient survival. Kaplan-Meier survival analysis was used to compare time-to-event outcomes. The investigators also explored whether shorter versus longer NRP exposure changed overall graft survival and performed subgroup analyses for patients at higher risk.
Main Findings
After matching, NRP was associated with better early recovery of transplanted kidneys. Delayed graft function occurred less often in the NRP group than in the non-NRP group, 30.3% versus 49.7%. In practical terms, this means kidneys were less likely to need dialysis in the first days after transplant, which is an important marker of early graft stress.
NRP was also associated with a shorter hospital stay, with a median of 4 days compared with 5 days in the non-NRP group. Although a one-day difference may seem modest, across a large transplant program this can reflect smoother recovery, fewer early complications, and lower resource use.
Beyond early recovery, NRP was linked to improved overall graft survival and patient survival, with statistically significant differences reported for both outcomes. The study also found benefit in overall graft and patient survival over the follow-up period, including 3-year and overall outcomes.
Importantly, the investigators did not find a significant difference in overall graft survival between shorter and longer NRP durations. This suggests that once NRP is applied within the studied range, extending the duration may not provide additional graft-survival benefit. In other words, the presence of NRP mattered more than the exact length of NRP in this analysis.
Who Benefited Most
Subgroup analysis showed that the protective effect of NRP was more pronounced in higher-risk transplants. The benefit was especially evident in cases involving older recipients or older donors, donors with higher body mass index, kidneys with a higher Kidney Donor Profile Index, and recipients who had undergone prolonged dialysis before transplantation.
These findings make clinical sense. Older or marginal organs are more vulnerable to ischemic injury, and recipients with a longer dialysis history may have more complicated pretransplant conditions. For these groups, improving organ oxygenation before procurement may help reduce the impact of warm ischemia and improve the chances of early and sustained graft function.
Clinical Interpretation
The study provides strong real-world evidence that NRP can improve both early and mid-term outcomes after DCD kidney transplantation. The reduction in delayed graft function is particularly meaningful because delayed graft function is not just an inconvenience; it is associated with more complex post-operative care, longer hospitalization, and potentially worse long-term graft health.
The observed survival benefit is also important because it suggests that NRP may help not only with immediate kidney function but also with the durability of the transplanted organ and the health of the recipient over time. For transplant teams, this may support broader consideration of NRP in DCD procurement workflows, especially when donor risk factors suggest a kidney may be more susceptible to ischemic injury.
At the same time, the study should be interpreted with the usual caution applied to observational data. Even with propensity score matching, unmeasured differences between groups may remain. The analysis was based on registry data, which are powerful for capturing large numbers of cases but can lack granular details such as exact technical variations, center-level practice patterns, perfusion protocols, and some perioperative variables. In addition, the study examined transplants performed in a relatively recent era, so longer-term outcomes beyond the available follow-up still need to be studied.
Why This Matters
The use of DCD donors is one way to expand the kidney transplant donor pool and reduce wait-list mortality. However, DCD kidneys are often at higher risk of ischemic damage than kidneys recovered after brain death. Strategies such as NRP may help make more DCD kidneys usable and improve their performance after transplant.
If confirmed in future prospective studies, these findings could influence organ procurement policy and transplant center protocols. They also suggest that the value of NRP may be greatest in challenging transplant scenarios, where the organ is already at higher risk. That could help centers prioritize resources and refine donor-selection and preservation strategies.
Limitations and Future Directions
Although the findings are encouraging, several questions remain. The optimal NRP protocol, including ideal timing and duration, is still not fully established. The lack of a survival difference between shorter and longer NRP in this study suggests that “more” NRP may not necessarily be better, but future work should test this in controlled settings.
Further research should also explore mechanisms more directly, including whether NRP reduces inflammatory injury, improves microcirculation, or better preserves tubular cell integrity. Studies that include detailed perfusion parameters, histologic findings, and center-specific practice data could help define which components of NRP drive benefit.
Finally, as transplant programs continue to adopt NRP, long-term follow-up will be essential to determine whether the early and mid-term advantages observed here translate into durable graft function over 5 years and beyond.
Conclusion
In this large U.S. nationwide analysis of adult primary DCD kidney transplants, normothermic regional perfusion was associated with less delayed graft function, shorter hospitalization, and better overall graft and patient survival. The benefit did not appear to depend strongly on NRP duration within the studied range. The strongest advantages were seen in higher-risk donor and recipient subgroups.
Overall, the study supports NRP as a promising approach to improving outcomes in kidney transplantation from DCD donors, particularly when the goal is to protect marginal organs and optimize transplant success.
