Donation After Circulatory Death Kidney Transplantation Research Articles

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation. SNMP at 22-25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys. In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs. These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.

Waitlist and Transplant Outcomes in Organ Donation After Circulatory Death: Trends in the United States.

To summarize waitlist and transplant outcomes in kidney, liver, lung, and heart transplantation using organ donation after circulatory death (DCD). DCD has expanded the donor pool for solid organ transplantation, most recently for heart transplantation. The United Network for Organ Sharing registry was used to identify adult transplant candidates and recipients in the most recent allocation policy eras for kidney, liver, lung, and heart transplantation. Transplant candidates and recipients were grouped by acceptance criteria for DCD versus brain-dead donors [donation after brain death (DBD)] only and DCD versus DBD transplant, respectively. Propensity matching and competing-risks regression was used to model waitlist outcomes. Survival was modeled using propensity matching and Kaplan-Meier and Cox regression analysis. DCD transplant volumes have increased significantly across all organs. Liver candidates listed for DCD organs were more likely to undergo transplantation compared with propensity-matched candidates listed for DBD only, and heart and liver transplant candidates listed for DCD were less likely to experience death or clinical deterioration requiring waitlist inactivation. Propensity-matched DCD recipients demonstrated an increased mortality risk up to 5 years after liver and kidney transplantation and up to 3 years after lung transplantation compared with DBD. There was no difference in 1-year mortality between DCD and DBD heart transplantation. DCD continues to expand access to transplantation and improves waitlist outcomes for liver and heart transplant candidates. Despite an increased risk for mortality with DCD kidney, liver, and lung transplantation, survival with DCD transplant remains acceptable.

Metabolic Outcomes After Pancreas Transplant Alone From Donation After Circulatory Death Donors-The UK Transplant Registry Analysis.

Extrapolating data from early DCD (donation after circulatory death) kidney transplantation, pancreas transplants from DCD grafts were feared to have worse metabolic outcomes. Hence, we aimed to address the question of pancreas transplant alone (PTA) from DCD donors-are our concerns justified? A UK transplant registry analysis of 185 PTA performed between 2005 and 2018 was done. All early graft losses (<3months) were excluded to allow focus on the metabolic outcomes (HbA1c, weight gain and incidence of secondary diabetic macrovascular complications). The aim was to compare the metabolic outcomes, rejection rates (including the need for steroids), patient and graft survival between DBD (Donation after brainstem death) and DCD groups. After excluding early graft losses, data from 162 PTA (DBD = 114 and DCD = 48) were analyzed. Body mass index of the donor was less in DCD group (DBD = 23.40 vs. DCD = 22.25, p = 0.006) and the rest of the baseline transplant characteristics were comparable. There were no significant differences in the HbA1c, weight gain, rejection rate, and incidence of secondary diabetic macrovascular complications post-transplant between DBD and DCD recipients. The 1-, 5-, and 10-year patient and graft survival were similar in both the groups. PTA from DCD donors have equivalent metabolic outcomes and survival (patient/graft) as that of DBD donors.

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs

The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p=0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p=0.24 and 0.79 respectively). Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.

Normothermic Regional Perfusion Can Improve Both Utilization and Outcomes in DCD Liver, Kidney, and Pancreas Transplantation.

Using the US national registry data between 2020 and 2021, donation after circulatory death (DCD) donors were separated into 2 groups: DCD with TA-NRP and without TA-NRP. There were 5234 DCD donors; among them 34 donors were with TA-NRP. After 1:4 propensity score matching, the utilization rates were compared between DCD with and without TA-NRP. Although the utilization rates of kidney and pancreas were comparable (P = 0.71 and P = 0.06, 94.1% versus 95.6% and 8.8% versus 2.2%, respectively), that of liver in DCD with TA-NRP was significantly higher (P < 0.001; 70.6% versus 39.0%). Among 24 liver transplantations, 62 kidney transplantations, and 3 pancreas transplantations from DCD with TA-NRP, there were 2 liver grafts and 1 kidney graft that failed within 1 y after transplantation. TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes.

Outcomes of DCD kidneys with CIT-induced delayed graft function.

Donation after circulatory death (DCD) kidneys are exposed to warm ischemia, which, coupled with cold ischemia time (CIT) exacerbates delayed graft function (DGF) and is possibly associated with worse graft survival. To analyze the risk of CIT-induced DGF on DCD kidney outcomes, we evaluated national data between 2008 and 2018 of adult kidney-only recipients of paired DCD kidneys where one kidney recipient experienced DGF and the other did not. Of 5602 paired DCD kidney recipients, multivariate analysis between recipients with higher CIT relative to lower CIT showed that increasing CIT differences had a significant dose-dependent effect on overall graft survival. The graft survival risk was minimal with CIT differences of ≥1-h (adjusted hazard ratio [aHR] 1.07, 95% CI .95- 1.20, n = 5602) and ≥5-h (aHR 1.09, 95% CI .93-1.29, n = 2710) and became significant at CIT differences of ≥10-h (aHR 1.37, 95% CI 1.05-1.78, n = 1086) and ≥15-h (aHR 1.78, 95% CI 1.15-2.77, n = 1086). Between each of the four delta-CIT levels of shorter and longer CIT, there were no statistically significant differences in the proportion of acute rejection. These results suggest that in the setting of DCD kidney transplantation (KTX), DGF, specifically mediated by prolonged CIT, impacts long-term graft outcomes.

DCD kidney transplantation in Italy: Past, present, and future

The disproportion between the number of patients on the kidney transplant waiting list and the actual donors pool represents a primary issue for the international Transplant community. The development of donation after circulatory death (DCD) programs has been associated with a remarkable increase in organs procurement and transplants activities across the globe. However, effective DCD donation and transplantation require the resolution of several legal, ethical, deontological, logistical, and technical issues. In Italy, the major obstacle to this very specific type of dation was represented by the 20-minute no-touch period for the declaration of death by cardio-circulatory criteria established by the Italian legislation. Following the encouraging results obtained with the use of in situ Normothermic Regional Perfusion in the setting of a single-center exploratory trial performed between 2008 and 2013 (Alba project), the Comitato Nazionale per la Bioetica and the Centro Nazionale Trapianti eventually managed to start a national-scale controlled and uncontrolled DCD program. We herein describe the Italian DCD KT program with a special focus on the most crucial and peculiar aspects of the national organ donation and allocation process.

O006 A randomised trial of normothermic machine perfusion versus static cold storage in donation after circulatory death renal transplantation

Abstract Introduction Kidneys from donation after circulatory death (DCD) donors are more susceptible to cold storage (CS) injury and have a high risk of delayed graft function (DGF). This trial is the first to compare normothermic machine perfusion (NMP) to conventional CS in DCD kidney transplantation. Methods In a multicentre randomised control trial, DCD kidneys were randomised to either NMP or CS. NMP kidneys were perfused for 60min with an oxygenated red-cell-based solution (36.0°C) The primary end point was DGF defined as the requirement for dialysis in the first 7days post-transplant. Secondary outcome measures included renal function up to 12 months posttransplant and patient/ graft survival. For all outcome measures a logistic regression model was used adjusted for cold ischaemic time, donor age, left/right kidney and centre. Results February 2016-March 2020, 338 kidneys were randomised into the trial. Twenty-five kidneys did not undergo NMP due to logistical/technical difficulties but were included in an intention-to-treat analysis. Twenty-seven kidneys in the NMP and 21 in the CS group where not transplanted and excluded; 143 NMP and 147 CS kidneys were analysed. There was no significant difference in the rate of DGF (NMP 61% vs CS 58%; P=0.624). Secondary outcome measures demonstrated a significantly higher creatinine reduction ratio day 2(CRR2) (P=0.035) and significantly lower levels of serum creatinine across all timepoints in the NMP group (P=0.024). Conclusion A short end period of NMP did not reduce rates of DGF in DCD kidneys. Secondary outcome measures suggest that NMP may improve renal function. Take-home message This is the first randomised controlled trial of normothermic machine perfusion (NMP) in clinical transplantation. The results suggest that NMP may improve the renal function of DCD kidneys.

Anastomosis Time and Outcomes after Donation after Circulatory Death Kidney Transplantation.

At every stage in the transplantation process for a deceased-donor kidney, time means ischemia. Donation after circulatory death (DCD) kidneys are already subject to warm ischemia in the donor, but another underappreciated component of warm ischemia time is the time required for anastomosis prior to reperfusion. We studied the effect of anastomosis time (AT) on outcomes after DCD kidney transplantation. This is a retrospective study of the Scientific Registry of Transplant Recipients, including all US adult DCD kidney transplantation recipients from 2009 to 2015 (N = 6,397). Our exposure was AT (time out of cold storage until reperfusion, quartiles). Outcomes included delayed graft function (DGF), death-censored graft survival, and overall patient survival. Multivariable logistic and Cox regression quantified the association of AT with outcomes, adjusting for donor and recipient factors (including donor warm ischemia time). AT accounted for 67% of total warm ischemia time on average, with a median AT of 38 minutes (median total warm ischemia 56 minutes). Longer AT (fourth [≥48min] vs first quartile [≤30min]) was associated with increased DGF (odds ratio = 1.19, p = 0.024) and increased graft failure (hazard ratio = 1.21, p = 0.043) but was not associated with patient survival. Comparing patients with the longest vs shortest AT, adjusted DGF incidence was 44.0% vs 36.7% (p = 0.024), and 5-year graft survival was 84.8% vs 88.2% (p = 0.004). Prolonged AT is associated with worse graft outcomes in DCD kidney transplant recipients. Efforts to minimize rewarming during implantation and optimize AT may improve graft outcomes.

Effect of Ischemia Times and Donor and Recipient Features on Maastricht Category III Kidney Transplant Outcomes.

Expansion of the donor pool has been enabled by the use of donation after circulatory death (DCD). The aim of this study is to identify what donation features are able to predict kidney transplant (KT) outcomes from DCD. A prospective analysis of all DCD KT from June 2016 to November 2019 was conducted. Association between donor and recipient features, and ischemia times with delayed graft function (DGF) and serum creatinine (Cr) at discharge, and at three and twelve months were analysed. A total of 86 KT were performed. The results revealed a relationship between donor age (p = 0.014) and receptors on haemodialysis (p = 0.001) with DGF. There was no association between different ischemia times and DGF. Residual urine output greater than 500mL/day and being on peritoneal dialysis were found to be protective factors for DGF. Correlation analysis illustrated a significant correlation between donor age and Cr at discharge and at 3 months. Higher donor age and being on haemodialysis were risk factors for DGF. Likewise, donor age did not show a significant association with 12-month serum Cr. These results demonstrate that donor age is a risk factor for DGF but does not affect long term graft function.

Prolonged Normothermic Ex Vivo Kidney Perfusion Is Superior to Cold Nonoxygenated and Oxygenated Machine Perfusion for the Preservation of DCD Porcine Kidney Grafts.

Background.The increased usage of marginal grafts has triggered interest in perfused kidney preservation to minimize graft injury. We used a donation after circulatory death (DCD) porcine kidney autotransplantation model to compare 3 of the most frequently used ex vivo kidney perfusion techniques: nonoxygenated hypothermic machine perfusion (non-oxHMP), oxygenated hypothermic machine perfusion (oxHMP), and normothermic ex vivo kidney perfusion (NEVKP).Methods.Following 30 min of warm ischemia, grafts were retrieved and preserved with either 16 h of non-oxHMP, oxHMP, or NEVKP (n = 5 per group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed for 8 d. Kidney function and injury markers were compared between groups.Results.NEVKP demonstrated a significant reduction in preservation injury compared with either cold preservation method. Grafts preserved by NEVKP showed superior function with lower peak serum creatinine (NEVKP versus non-oxHMP versus oxHMP: 3.66 ± 1.33 mg/dL, 8.82 ± 3.17 mg/dL, and 9.02 ± 5.5 mg/dL) and more rapid recovery. The NEVKP group demonstrated significantly increased creatinine clearance on postoperative day 3 compared with the cold perfused groups. Tubular injury scores on postoperative day 8 were similar in all groups.Conclusions.Addition of oxygen during HMP did not reduce preservation injury of DCD kidney grafts. Grafts preserved with prolonged NEVKP demonstrated superior initial graft function compared with grafts preserved with non-oxHMP or oxHMP in a model of pig DCD kidney transplantation.

Donor-Recipient BSA Matching Is Prognostically Significant in Solitary and En Bloc Kidney Transplantation From Pediatric Circulatory Death Donors.

Background.As the rate of early postoperative complications decline after transplant with pediatric donation after circulatory death (DCD) kidneys, attention has shifted to the long-term consequences of donor–recipient (D-R) size disparity given the pernicious systemic effects of inadequate functional nephron mass.Methods.We conducted a retrospective cohort study using Organ Procurement and Transplantation Network data for all adult (aged ≥18 y) recipients of pediatric (aged 0–17 y) DCD kidneys in the United States from January 1, 2004 to March 10, 2020.Results.DCD pediatric allografts transplanted between D-R pairs with a body surface area (BSA) ratio of 0.10–0.70 carried an increased risk of all-cause graft failure (relative risk [RR], 1.36; 95% confidence interval [CI], 1.10–1.69) and patient death (RR, 1.32; 95% CI, 1.01–1.73) when compared with pairings with a ratio of >0.91. Conversely, similar graft and patient survivals were demonstrated among the >0.70–0.91 and >0.91 cohorts. Furthermore, we found no difference in death-censored graft survival between all groups. Survival analysis revealed improved 10-y patient survival in recipients of en bloc allografts (P = 0.02) compared with recipients of single kidneys with D-R BSA ratios of 0.10–0.70. A similar survival advantage was demonstrated in recipients of solitary allografts with D-R BSA ratios >0.70 compared with the 0.10–0.70 cohort (P = 0.02).Conclusions.Inferior patient survival is likely associated with systemic sequelae of insufficient renal functional capacity in size-disparate DCD kidney recipients, which can be overcome by appropriate BSA matching or en bloc transplantation. We therefore suggest that in DCD kidney transplantation, D-R BSA ratios of 0.10–0.70 serve as criteria for en bloc allocation or alternative recipient selection to optimize the D-R BSA ratio to >0.70.

Urinary TIMP-2 Predicts the Presence and Duration of Delayed Graft Function in Donation After Circulatory Death Kidney Transplant Recipients.

Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients. Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression. Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF. Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study.

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n=9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.75)days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1year, and a higher rate of acute rejection. On Kaplan-Meier analysis, the presence of DGF was associated with lower graft survival (log-rank test P=0.034), though duration of DGF was not (P=0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617-11.450); P=0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients.

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty-seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N=53) vis-à-vis the group without fDGF (N=22). In those with prolonged fDGF (≥21days) (N=17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21days) (N=36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched-chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.

Comparison of outcomes of kidney transplantation from donation after brain death, donation after circulatory death, and donation after brain death followed by circulatory death donors.

There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors. We retrospectively reviewed 469 recipients who received deceased kidney transplantation in our hospital from February 2007 to June 2015. The recipients were divided into three groups according to the source of their donor kidneys: DBD, DCD, or DBCD. The primary endpoints were delayed graft function (DGF), graft loss, and patient death. The warm ischemia time was much longer in DCD group compared to DBCD group (18.4minutes vs 12.9minutes, P<.001). DGF rate was higher in DCD group than in DBD and DBCD groups (22.5% vs 10.2% and 13.8%, respectively, P=.021). Urinary leakage was much higher in DCD group (P=.049). Kaplan-Meier analysis showed that 1-, 2-, and 3-year patient survivals were all comparable among the three groups. DBCD kidney transplantation has lower incidences of DGF and urinary leakage than DCD kidney transplant. However, the overall patient and graft survival were comparable among DBD, DCD, and DBCD kidney transplantation.

UK National Registry Study of Kidney Donation After Circulatory Death for Pediatric Recipients.

Donation after circulatory death (DCD) kidney transplantation has acceptable renal allograft survival in adults but there are few data in pediatric recipients. The aim of this study was to determine renal allograft outcomes for pediatric recipients of a DCD kidney. Data were collected from the UK Transplant Registry held by National Health Service Blood and Transplant. Kidney transplants performed for pediatric recipients (age, <18 years) in the United Kingdom from 2000 to 2014 were separated into DCD, donation after brain death (DBD), and living donor (LD) transplants, analyzing 3-year patient and renal allograft survival. One thousand seven hundred seventy-two kidney only transplants were analyzed. Twenty-one (1.2%) of these were from DCD donors, 955 (53.9%) from DBD donors, and 796 (44.9%) from LDs. Patient survival is 100% in the DCD group, 98.7% in the DBD group, and 98.9% in the LD group. Three-year renal allograft survival was 95.2% in the DCD group, 87.1% in the DBD group, and 92.9% in the LD group. There was no significant difference in 3-year renal allograft survival between the DCD and DBD groups (P = 0.42) or DCD and LD groups (P = 0.84). For DCD, the primary nonfunction rate was 5% and delayed graft function was 25%. Children receiving a DCD kidney transplant have good renal allograft survival at 3-year follow-up, comparable to those receiving a kidney from a DBD donor or a LD. This limited evidence encourages the use of selected DCD kidneys in pediatric transplantation, and DCD allocation algorithms may need to be reviewed in view of this.

Pathophysiological Trends During Withdrawal of Life Support: Implications for Organ Donation After Circulatory Death.

Donation after circulatory death (DCD) provides an alternative pathway to deceased organ transplantation. Although clinical DCD lung, liver, and kidney transplantation are well established, transplantation of hearts retrieved from DCD donors has reached clinical translation only recently. Progress has been limited by concern regarding the viability of DCD hearts. The aim of this study was to document the pathophysiological changes that occur in the heart and circulation during withdrawal of life (WLS) support. In a porcine asphyxia model, we characterized the hemodynamic, volumetric, metabolic, biochemical, and endocrine changes after WLS for up to 40 minutes. Times to circulatory arrest and electrical asystole were recorded. After WLS, there was rapid onset of profound hypoxemia resulting in acute pulmonary hypertension and right ventricular distension. Concurrently, progressive systemic hypotension occurred with a fall in left atrial pressure and little change in left ventricular volume. Mean times to circulatory arrest and electrical asystole were 8 ± 1 and 16 ± 2 minutes, respectively. Hemodynamic changes were accompanied by a rapid fall in pH, and rise in blood lactate, troponin-T, and potassium. Plasma noradrenaline and adrenaline levels rose rapidly with dramatic increases in coronary sinus levels indicative of myocardial release. These findings provide insight into the nature and tempo of the damaging events that occur in the heart and in particular the right ventricle during WLS, and give an indication of the limited timeframe for the implementation of potential postmortem interventions that could be applied to improve organ viability.

Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation.

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS.