The Benefit of Sequential Normothermic Regional Perfusion and Hypothermic Machine Perfusion in Kidney Transplantation From Donation After Circulatory Death Donors

ABSTRACT

Background

Normothermic regional perfusion (NRP) is associated with improved posttransplant outcomes in donation after circulatory death (DCD) kidney transplantation. It remains unknown whether hypothermic machine perfusion (HMP) offers additional benefits over static cold storage (SCS) during transport.

Methods

All adult kidney‐only transplantations from DCD donors procured by NRP in the OPTN data (10/1/2020‐6/30/2025) were identified. Primary exposure was preservation method during transport: NRP combined with HMP (NRP+HMP) or SCS (NRP+SCS). One‐to‐two propensity score matching (PSM) was performed on fifteen donor and recipient factors. Primary outcomes included delayed graft function (DGF), posttransplant length of stay (LOS), and estimated glomerular filtration rate (eGFR) at 6 months posttransplant. Secondary outcomes were one‐year graft and patient survival.

Results

Among 4792 NRP cases, HMP was utilized in 85.1%, with its use increasing over time. After 1:2 PSM (685 NRP+SCS matched to 1262 NRP+HMP), NRP+HMP was associated with significantly lower DGF (23.3% vs. 30.5%, p < 0.01). Median LOS (4.0 days in both groups, p = 0.07), 6‐month eGFR (58.5 vs. 60.1 mL/min/1.73m², p = 0.46), one‐year graft survival, and one‐year patient survival were not significantly different. The association between HMP and lower DGF was observed across KDPI strata, heart recovery status, and cold ischemia time categories, with no significant interactions detected.

Conclusion

The adoption of HMP after NRP has increased substantially in the United States and was associated with reduced DGF, but no difference was observed for LOS, 6‐month eGFR, graft survival, and patient survival. These findings support the routine use of HMP after NRP.

Abbreviations

A‐NRP

Abdominal NRP

ASTS

American Society of Transplant Surgeons

DBD

Donation after Brain Death

DCD

Donation after Circulatory Death

DGF

Delayed Graft Function

Egfr

estimated glomerular filtration rate

EPTS

Estimated Post Transplant Survival

HMP

Hypothermic Machine Perfusion

KDPI

Kidney Donor Profile Index

LOS

Length of Stay

NRP

Normothermic Regional Perfusion

OPTN

Organ Procurement and Transplantation Network

SCS

Static Cold Storage

SMD

Standardized Mean Differences

SRR

Standard Rapid Recovery

TA‐NRP

Thoraco‐Abdominal NRP

UNOS

United Network for Organ Sharing.

1. Introduction

Kidney transplantation (KT) is the definitive treatment for end‐stage renal disease [1]. However, the demand has far outweighed the supply for the past three decades in the United States. In 2023, 141 886 adult candidates were on the waitlist for deceased donor kidneys, while the number of adult KT was 27 351 [2]. To address this gap, donation after circulatory death (DCD) donors have increasingly been utilized [3, 4]. When DCD kidneys are procured with standard rapid recovery (SRR) and preserved with static cold storage (SCS), they are prone to ischemic reperfusion injury, thus leading to higher rates of delayed graft function (DGF) [5]. The use of hypothermic machine perfusion (HMP) is associated with a decreased DGF in DCD KT, but only to a modest extent (53.7% vs. 69.5%) [6].

Recently, with the advent of normothermic regional perfusion (NRP), the outcomes of DCD KT have further improved [7], achieving lower incidence of DGF than SRR (30% in NRP vs. 48% in SRR) [8], or even lower than donation after brain death (DBD) donors (20% in NRP vs. 28% in DBD) [9]. These superior outcomes of DCD kidneys procured by NRP over those procured by SRR have led to NRP being made mandatory for DCD donors in France, Italy, and Norway [9, 10, 11]. In the United States, NRP implementation started in 2020, and, its use spread tremendously after American Society of Transplant Surgeons (ASTS) included NRP in its recommendations in 2023 [12, 13]. Initially, NRP in the United States was mainly performed in donors involving heart procurement in the form of thoraco‐abdominal NRP (TA‐NRP) with significant reduction in DGF (13%–14% in TA‐NRP vs. 42%–44% in SRR) [14, 15, 16], but more recently many transplant centers have started using abdominal NRP (A‐NRP) [14, 15].

As NRP has been increasingly adopted, it is also being used more often in higher‐risk donors with comorbidities such as hypertension and diabetes. Although DCD kidneys procured with NRP have a similar incidence of DGF as DBD kidneys, the incidence of DGF is expected to be increased for higher risk kidneys, which are more often procured using NRP. Even with NRP, DCD kidneys preserved with SCS are subject to ischemic reperfusion injury during transport, which may be mitigated by HMP. Since the use of HMP is associated with decreased DGF for extended criteria DBD donors [17], and the NRP outcomes in countries with mandatory HMP are even better than those of DBD KT [9], we hypothesized that the incidence of DGF will be lower in high‐risk kidneys when HMP was employed after NRP (NRP+HMP) compared to SCS (NRP+SCS). The aim of this study was to characterize the use of HMP in DCD‐NRP KT in the United States and assess whether the use of HMP was associated with a clinical benefit, using the Organ Procurement and Transplantation Network (OPTN) database.

2. Materials and Methods

2.1. Study Population

The study utilized data from the OPTN Standard Transplant Analysis and Research file. The study cohort consisted of adult (age ≥ 18 years) recipients who underwent kidney‐only transplantation from DCD donors procured by NRP between October 2020 and June 2025. These dates were chosen as the period following the first NRP DCD procurement in the United States [13]. The last day of follow‐up was January 2, 2026. Using a previously described method, the use of NRP during procurement was identified when death to cross‐clamp time ≥30 min [12]. Candidates with missing values for cold ischemia time, donor creatinine, donor weight, and DGF were excluded. The study, consisting of analysis of deidentified data, was deemed exempt by the institutional review board at Stanford University.

2.2. Exposures and Outcomes

The study cohort was classified into NRP+HMP or NRP+SCS by the use of HMP during transport. The temporal trends in the use of sequential NRP and HMP in deceased donor KT were evaluated. We selected three primary outcomes: DGF, defined by the need for dialysis within the first seven days posttransplant; median length of hospital stay (LOS); and eGFR at six months posttransplant. The secondary outcomes were one‐year graft and patient survival. Subgroup analyses were performed by dividing the study cohort into Kidney Donor Profile Index (KDPI) strata (0%–20%, 21%–49%, 50%–85%, and 86%–100%), by concomitant heart recovery (heart donors or non‐heart donors), or by cold ischemia time (<18, 18–24, and ≥24 h). Furthermore, the proportion of patients with 30‐day graft loss and the reported primary causes of early graft failure were examined descriptively.

2.3. Statistical Analysis

Statistical analyses were conducted using R 4.5.0 (https://cran.r‐project.org/). Donor and recipient demographics were presented as frequencies with percentages or median values with interquartile ranges. Differences between categorical values were assessed using the chi‐square test, while continuous values were analyzed using the Mann–Whitney U or Kruskal–Wallis tests, as applicable. Estimated GFR was calculated as defined by the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) 2021 [18]. One‐year graft and patient survival were evaluated using the Kaplan–Meier method and the log‐rank test. Graft survival was calculated from date of transplant until death, graft loss, or the last recorded follow‐up. One‐to‐two nearest neighbor propensity score matching (1:2 PSM) with a caliper of 0.20 was employed using the R package “MatchIt” to balance the two groups by adjusting for donor factors included in KDPI (age, height, weight, hypertension, diabetes, cause of death, creatinine) [19], donor sex, recipient factors included in EPTS (age, dialysis before transplant, diabetes, the number of previous transplants) [20], concomitant heart recovery, etiology of kidney disease, and cold ischemia time. SMD were estimated before and after matching; SMD < 0.1 indicates good balance [21, 22]. Because HMP is expected to primarily mitigate ischemia‐reperfusion injury and thereby influence graft function, we assessed whether the associations of HMP use with DGF and graft survival differed according to donor kidney quality and concomitant heart recovery. In the matched cohort, interaction terms between HMP use and KDPI category, between HMP use and heart recovery status, and between HMP use and cold ischemia time category were tested using logistic regression for DGF and Cox regression for graft survival. For all analyses, statistical significance was established below a p‐value of 0.05.

3. Results

3.1. Temporal Trends in the Use of HMP With NRP

There were 4792 recipients in the study cohort after excluding patients with missing values for cold ischemia time, donor creatinine, donor weight, and DGF. Among them, 4077 (85.1%) and 715 (14.9%) KT were classified as NRP+HMP and NRP+SCS, respectively. The number of KT using NRP significantly increased over the study period (Figure 1). NRP+HMP for donors with concomitant heart recovery was most common until 2022; afterwards, NRP+HMP for donors without concomitant heart recovery became the most common, comprising 76.4% (1384 out of 1812 cases) in 2025.

FIGURE 1.

Trends in the number of DCD KT using NRP. Abbreviations: DCD, donation after circulatory death; HMP, hypothermic machine perfusion; NRP, normothermic regional perfusion; SCS, static cold storage.

3.2. Baseline Characteristics

Before matching, donor and recipient characteristics differed between the NRP+SCS and NRP+HMP groups (Table 1). Compared to the NRP+SCS donors, the NRP+HMP donors were older, less likely to be male, more likely to have hypertension, more likely to have diabetes, less likely to have heart recovered, had longer cold ischemia time, and had higher KDPI. A total of 517 donors (10.8% out of the study cohort, 487 in the NRP+HMP group and 30 in the NRP+SCS group) had KDPI >85%. Compared to the NRP+SCS recipients, the NRP+HMP recipients were older, more likely to have diabetes, and had higher EPTS score. After 1:2 PSM, 685 NRP+SCS KTs were matched to 1262 NRP+HMP KTs. The baseline characteristics of the matched cohorts are shown (Table 2). All SMDs for matched covariates were below 0.10 after matching.

TABLE 1.

Baseline characteristics in the unmatched cohort.

Variable	NRP+SCS N = 715 a	NRP+HMP N = 4077 a	p‐value b	SMD
Donor age, years	36.0 [26.0, 46.0]	47.0 [36.0, 58.0]	<0.001	0.701
Donor sex			<0.001	0.207
Female	165 (23.1%)	1317 (32.3%)
Male	550 (76.9%)	2760 (67.7%)
Donor height, cm	174.0 [165.0, 180.0]	173.0 [165.0, 180.0]	0.209	0.140
Donor weight, kg	83.4 [69.5, 98.8]	85.0 [72.0, 101.0]	0.002	0.191
Donor hypertension	174 (24.3%)	1627 (39.9%)	<0.001	0.338
Donor diabetes	37 (5.2%)	525 (12.9%)	<0.001	0.271
Donor creatinine, mg/dL	0.72 [0.55, 0.99]	0.80 [0.60, 1.19]	<0.001	0.307
Cause of death			<0.001	0.236
Anoxia	328 (45.9%)	2069 (50.7%)
Cerebrovascular/stroke	114 (15.9%)	790 (19.4%)
Head trauma	232 (32.4%)	907 (22.2%)
CNS tumor	1 (0.1%)	7 (0.2%)
Other	40 (5.6%)	304 (7.5%)
Concomitant heart recovery	374 (52.3%)	1072 (26.3%)	<0.001	0.553
Cold ischemia time, hours	17.5 [13.5, 21.2]	20.2 [17.0, 23.7]	<0.001	0.547
Distance, nautical miles	146.0 [42.0, 225.0]	108.0 [28.0, 203.0]	<0.001	0.162
KDPI	0.34 [0.21, 0.55]	0.53 [0.34, 0.75]	<0.001	0.613
Primary diagnosis			<0.001	0.258
Cystic kidney disease	29 (4.1%)	257 (6.3%)
Diabetes	203 (28.4%)	1506 (36.9%)
Glomerulonephritis	146 (20.4%)	558 (13.7%)
Hypertension	162 (22.7%)	918 (22.5%)
Others	175 (24.5%)	838 (20.6%)
Recipient age, years	53.0 [41.0, 63.0]	59.0 [50.0, 67.0]	<0.001	0.432
Recipient sex			0.397	0.034
Female	288 (40.3%)	1574 (38.6%)
Male	427 (59.7%)	2503 (61.4%)
Recipient BMI, kg/m2	27.7 [23.9, 31.9]	28.2 [24.6, 32.2]	0.023	0.100
Dialysis before transplant	590 (82.5%)	3406 (83.5%)	0.497	0.027
Recipient diabetes	254 (35.5%)	1881 (46.1%)	<0.001	0.217
EPTS score	0.42 [0.16, 0.71]	0.59 [0.32, 0.82]	<0.001	0.384

Abbreviations: BMI, body mass index; CNS, central nervous system; EPTS, estimated posttransplant survival; KDPI, kidney donor profile index; SMD, standardized mean difference.

^a Median [Q1, Q3]; n (%).

^b Wilcoxon rank sum test; Pearson's Chi‐squared test.

TABLE 2.

Baseline characteristics in the matched cohort.

Variable	NRP+SCS N = 685 a	NRP+HMP N = 1262 a	p‐value b	SMD
Donor age, years	37.0 [27.0, 47.0]	38.0 [28.0, 48.0]	0.399	0.050
Donor sex			0.328	0.047
Female	160 (23.4%)	320 (25.4%)
Male	525 (76.6%)	942 (74.6%)
Donor height, cm	175.0 [166.0, 180.3]	173.0 [165.5, 180.0]	0.285	0.024
Donor weight, kg	84.0 [70.7, 99.7]	83.3 [69.8, 96.5]	0.331	0.010
Donor hypertension	174 (25.4%)	335 (26.5%)	0.583	0.026
Donor diabetes	37 (5.4%)	81 (6.4%)	0.369	0.043
Donor creatinine, mg/dL	0.73 [0.58, 0.99]	0.74 [0.56, 1.00]	0.679	0.071
Cause of death			0.985	0.029
Anoxia	311 (45.4%)	582 (46.1%)
Cerebrovascular/stroke	114 (16.6%)	216 (17.1%)
Head trauma	220 (32.1%)	396 (31.4%)
CNS tumor	1 (0.1%)	2 (0.2%)
Other	39 (5.7%)	66 (5.2%)
Concomitant heart recovery	353 (51.5%)	619 (49.0%)	0.295	0.050
Cold ischemia time, hours	17.6 [13.8, 21.2]	18.0 [14.9, 21.0]	0.056	0.092
Distance, nautical miles	146.0 [43.0, 226.0]	98.5 [20.0, 194.0]	<0.001	0.275
KDPI	0.34 [0.21, 0.55]	0.36 [0.22, 0.57]	0.225	0.048
Primary diagnosis			0.773	0.064
Cystic kidney disease	28 (4.1%)	62 (4.9%)
Diabetes	199 (29.1%)	374 (29.6%)
Glomerulonephritis	136 (19.9%)	231 (18.3%)
Hypertension	157 (22.9%)	305 (24.2%)
Others	165 (24.1%)	290 (23.0%)
Recipient age, years	53.0 [42.0, 63.0]	54.0 [42.0, 63.0]	0.397	0.036
Recipient sex			0.562	0.028
Female	273 (39.9%)	520 (41.2%)
Male	412 (60.1%)	742 (58.8%)
Recipient BMI, kg/m2	27.8 [24.1, 31.9]	28.0 [24.1, 32.3]	0.424	0.045
Dialysis before transplant	563 (82.2%)	1051 (83.3%)	0.542	0.029
Recipient diabetes	250 (36.5%)	477 (37.8%)	0.571	0.027
EPTS score	0.44 [0.18, 0.72]	0.47 [0.18, 0.76]	0.431	0.043

Abbreviations: BMI, body mass index; CNS, central nervous system; EPTS, estimated posttransplant survival; KDPI, kidney donor profile index; SMD, standardized mean difference.

^a Median [Q1, Q3]; n (%).

^b Wilcoxon rank sum test; Pearson's Chi‐squared test.

3.3. Immediate Posttransplant Outcomes

In the unmatched cohort, DGF (29.9% in NRP+HMP vs. 30.1% in NRP+SCS, p = 0.94) and LOS (4.0 days in both groups, p = 0.18) were not significantly different. In the matched cohort, NRP+HMP was associated with significantly lower DGF (23.3% vs. 30.5%, p < 0.01). Median LOS was 4.0 days in both groups (p = 0.07). Six‐month eGFR was not significantly different (58.5 vs. 60.1 mL/min/1.73m², p = 0.46). Thirty‐day graft loss was rare and not significantly different between groups (NRP+HMP, 12/1262 [1.0%] vs. NRP+SCS, 7/685 [1.0%]; p > 0.99). Graft loss attributed to primary nonfunction or graft thrombosis was also uncommon (6 vs. 3 events; 0.5% vs. 0.4%; p > 0.99).

When the matched cohort was stratified by KDPI strata, DGF rates were numerically lower in the NRP+HMP group across all KDPI strata, reaching statistical significance in the KDPI 0%–20% (10.7% vs. 18.9%, p = 0.024) and 50%–85% strata (32.6% vs. 44.1%, p = 0.015), but not in the 21%–49% (22.1% vs. 26.7%, p = 0.14) or 86%–100% strata (41.1% vs. 58.6%, p = 0.19) (Figure 2A). A formal test for interaction between HMP and KDPI strata was not statistically significant (p = 0.49). Median LOS (4.0 vs 4.0 days in KDPI 0%–20%, p = 0.26; 4.0 vs 4.0 days in KDPI 21%–49%, p = 0.23; 4.0 vs 5.0 days in KDPI 50%–85%, p = 0.43; and 5.0 vs 5.5 days in KDPI 86%–100%, p = 0.22) and median eGFR at 6 months (72.5 vs. 69.5 mL/min/1.73m² in KDPI 0%–20%, p = 0.56; 58.5 vs. 62.1 mL/min/1.73m² in KDPI 21%–49%, p = 0.13; 49.7 vs. 47.0 mL/min/1.73m² in KDPI 50%–85%, p = 0.21; and 43.8 vs. 41.0 mL/min/1.73m² in KDPI 86%–100%, p = 0.55) were not significantly different across KDPI strata (Figures 2B,C). When stratified by concomitant heart recovery, DGF rates were numerically lower in the NRP+HMP group in donors both with and without heart recovery, reaching statistical significance only in donors without heart recovery (28.3% vs. 40.4%, p < 0.001), but not in donors with heart recovery (18.1% vs. 21.2%, p = 0.27) (Figure S1A). A formal test for interaction between HMP and heart recovery was not statistically significant (p = 0.12). Median LOS was not significantly different in donors with heart recovery (4.0 vs 4.0 days, p = 0.82), but was shorter in the NRP+HMP group among donors without heart recovery (4.0 vs 5.0 days, p = 0.021). Median eGFR at 6 months was not significantly different in either group (63.7 vs. 67.4 mL/min/1.73m² in donors with heart recovery, p = 0.079; 53.3 vs. 50.3 mL/min/1.73m² in donors without heart recovery, p = 0.17) (Figure S1B,C). When the matched cohort was stratified by cold ischemia time, NRP+HMP was associated with significantly lower DGF in the <18 h group (19.8% vs. 27.1%, p = 0.009) and the 18–24 h group (26.0% vs. 35.7%, p = 0.009), but not in the ≥24 h group (30.0% vs. 30.7%, p > 0.99) (Figure S2A). A formal test for interaction between HMP and cold ischemia time was not statistically significant (p = 0.47). Median LOS and median eGFR at 6 months were not significantly different between the two groups across cold ischemia time categories, except for a shorter LOS in the NRP+HMP group within the <18 h category (p = 0.02) (Figure S2B,C).

FIGURE 2.

The incidence of DGF, LOS, and six‐month eGFR in the matched cohort divided by KDPI stratum. (A) The incidence of DGF in each KDPI stratum. (B) Median LOS in each KDPI stratum. (C) Median six‐month eGFR in each KDPI stratum. Abbreviations: DGF, delayed graft function; eGFR, estimated glomerular filtration rate; HMP, hypothermic machine perfusion; KDPI, kidney donor profile index; LOS, length of hospital stay; NRP, normothermic regional perfusion; SCS, static cold storage.

3.4. Graft and Patient Survival

In the unmatched cohort, one‐year graft survival (93.4% in NRP+HMP vs. 95.1% in NRP+SCS, p = 0.08) and patient survival (96.2% in NRP+HMP vs. 96.9% in NRP+SCS, p = 0.32) were not significantly different. In the matched cohort, one‐year graft survival (96.0% in NRP+HMP vs. 94.9% in NRP+SCS, p = 0.34) and patient survival (97.9% in NRP+HMP vs. 96.8% in NRP+SCS, p = 0.22) were not significantly different between the two groups (Figure 3A, Figure S3A). No significant interaction was detected between HMP and KDPI category (p = 0.87) and between HMP use and concomitant heart recovery (p = 0.93) for one‐year graft survival. Survival curves across KDPI strata and heart recovery status showed no substantial between‐group differences (Figures 3B–E, Figure S3B–E, Figure S4). No significant interaction was detected between HMP and cold ischemia time for one‐year graft survival (p = 0.30) or patient survival (p = 0.83) (Figure S5).

FIGURE 3.

Kaplan–Meier survival curves showing one‐year graft survival in the (A) overall, (B) subgroup of KDPI 0%–20%, (C) subgroup of KDPI 21%–49%, (D) subgroup of KDPI 50%–85%, (E) subgroup of KDPI 86%–100% of the matched cohort. Abbreviations: KDPI, kidney donor profile index.

4. Discussion

This study aimed to evaluate the benefits of subsequent HMP usage in KT from DCD donors recovered by NRP. With the use of NRP, DCD KT has been shown to achieve posttransplant outcomes similar to DBD, which has made NRP mandatory in France, Italy, and Norway [9, 10, 11, 23]. In the United States, NRP started in 2020, and its use has rapidly spread in the past few years. Theoretically, utilizing subsequent HMP after NRP protects kidneys from ischemic injury and further decreases immediate posttransplant complications such as DGF and longer LOS. The use of HMP with NRP is mandatory in France, but not in the United States, and its clinical benefit has been unclear. Our analysis revealed that the number of DCD KT using NRP has increased dramatically over the past few years. HMP was used in 85.1% of cases, and the 1:2 PSM revealed that HMP was associated with significantly lower DGF (23.3% vs. 30.5%, p < 0.01). No significant interaction was observed between HMP and KDPI strata (p = 0.49), indicating that the reduction in DGF was consistent regardless of donor kidney quality. LOS, eGFR at six months posttransplant, 1‐year graft survival, 1‐year patient survival, and 30‐day graft loss were not significantly different between NRP+HMP and NRP+SCS.

In earlier reports, the use of NRP for DCD procurement focused on TA‐NRP performed for donors whose hearts were procured [13, 14]. These donors are generally young with few comorbidities, with a median age and KDPI of 30 years and 20%, respectively [14]. Our analysis revealed that NRP for donors without heart recovery has significantly increased over the past few years, and HMP was used in the majority of these donors. The median age and KDPI in our overall NRP+HMP cohort were 47.0 years and 53%, which were older and higher than those in the NRP+SCS cohort or the previous report [14]. In this evolving landscape, it is important to evaluate the clinical benefit of adding HMP in DCD kidneys recovered using NRP, which theoretically reduces ischemic reperfusion injury and is routinely used in countries such as France with excellent outcomes.

In the matched cohort, NRP+HMP was associated with significantly lower DGF compared to NRP+SCS. Contrary to our initial hypothesis that HMP would be most beneficial in higher‐risk kidneys, the reduction in DGF was consistent across all KDPI strata without a significant interaction (p = 0.49). When stratified by cold ischemia time, NRP+HMP was associated with lower DGF in kidneys with cold ischemia time below 24 h, whereas no difference was observed beyond 24 h, although the interaction was not statistically significant and the ≥24 h subgroup was limited in size. Despite this reduction in DGF, one‐year graft and patient survival were not significantly different between the two groups, and 30‐day graft loss, including graft loss attributed to primary nonfunction or graft thrombosis, was rare in both groups. This dissociation between reduced DGF and unchanged eGFR or graft survival is consistent with prior HMP studies and may reflect short follow‐up, low graft‐loss event rates in NRP kidneys, and the heterogeneity of DGF as a binary endpoint. Prior studies suggest that prolonged DGF, rather than DGF occurrence alone, is more strongly associated with adverse graft outcomes [24, 25]. Nevertheless, reducing DGF remains clinically meaningful because it may lessen early posttransplant dialysis requirements, patient burden, and resource utilization. NRP itself substantially mitigates ischemia‐reperfusion injury during procurement, and has been shown to improve graft survival compared to SCS‐based recovery in DCD KT [26]. Against this already‐favorable baseline, the incremental benefit of adding HMP appears to lie in improving early graft function, most notably by reducing DGF, rather than in altering short‐term survival. This early functional benefit provides the primary clinical rationale for adding HMP in the NRP setting.

The high rate of HMP use in our cohort (85.1%) likely reflects not only outcome considerations but also logistical factors inherent to the United States transplant system. Unlike France, where NRP is performed in a geographically compact system with relatively short CIT (median 8.8 h) [23], the United States involves broad organ allocation across vast distances, resulting in prolonged cold ischemia times (median 20.2 h in our NRP+HMP cohort). Although machine perfusion during transport may be perceived as logistically demanding compared with SCS, HMP is already widely adopted in the United States, where it is used in approximately 80%–85% of DCD kidneys and by the majority of transplant centers, in part for the logistical flexibility it provides during long‐distance allocation and transport [27, 28]. In non‐NRP DCD transplantation, HMP has demonstrated cost‐effectiveness through DGF reduction and improved organ utilization, and it is reasonable to expect that at least some of these economic benefits would extend to NRP kidneys, although this remains to be formally demonstrated [29]. At the same time, both NRP and HMP carry their own costs in equipment, consumables, and personnel, which must be weighed against the savings from reduced DGF. Beyond direct cost, a lower expected risk of DGF may broaden equitable access to NRP kidneys. An anticipated high risk of DGF may discourage placement of a kidney into candidates for whom a posttransplant biopsy carries greater risk, such as those requiring anticoagulation; by lowering this risk, HMP could plausibly widen the range of suitable recipients. HMP may also facilitate allocation, as the additional ischemic time accrued during the acceptance process may be better tolerated by kidneys maintained on HMP, potentially making late‐declined organs more acceptable to subsequent centers. Taken together, the consistent reduction in DGF, together with these logistical and economic considerations, supports the routine use of HMP following NRP in the United States. Future studies evaluating long‐term graft survival and cost are warranted.

This study has several limitations. First, this is a retrospective study that relies on national registry data, which inherently carries the risk of bias due to inconsistent reporting among centers. Second, we used time from death to cross clamp to identify NRP as employed in multiple previous articles [12, 15], but there is no standardized variable in the OPTN database and there is a potential for misclassification. Third, among donors with concomitant heart recovery, the OPTN database does not capture whether the heart was procured via TA‐NRP or via A‐NRP combined with direct procurement, and we were unable to account for this distinction in our analysis. These two techniques may differ in their impact on kidney perfusion quality and DGF risk. Fourth, NRP in the United States is a relatively new practice in the past few years, and the impact of the addition of HMP on long‐term graft survival cannot be described here. Though the benefit of NRP+HMP compared to NRP+SCS seems to be in the improvement of short‐term outcomes including DGF, further research is needed to evaluate its impact on long‐term outcomes.

In conclusion, the sequential use of HMP in DCD kidneys recovered using NRP has become increasingly common in the United States and was associated with a significant reduction in DGF. No differences were observed in LOS, eGFR at six months posttransplant, graft survival, or patient survival. The consistent reduction in DGF, together with logistical considerations in the United States, supports the routine use of HMP after NRP.

Author Contributions

Participated in research design: Toshihiro Nakayama, Kliment K Bozhilov, Kazunari Sasaki. Participated in the writing of the paper: Toshihiro Nakayama, Kliment K Bozhilov, Kazunari Sasaki. Participated in the critical review: All authors. Participated in data analysis: Toshihiro Nakayama, Kliment K Bozhilov, Kazunari Sasaki.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

ctr70641‐sup‐0001‐tablesS1‐S5.docx

Data Availability Statement

The data reported here were supplied by United Network for Organ Sharing (UNOS) as the contractor for the OPTN. Access to the data is granted by UNOS upon reasonable request.