Donation After Circulatory Death Kidney Research Articles

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

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.

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP. Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed. Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger ( P < 0.001) and had lower Kidney Donor Profile Index ( P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger ( P < 0.001) and more likely to be blood group O ( P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival ( P = 0.8) and all-cause graft failure ( P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis. Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.

Successful transplantation of LUCAS device assisted uncontrolled DCD kidneys with prolonged relative warm ischemia time: An underutilized option in North America.

Approximately 25% of deceased donors in the United States are procured in a donation after circulatory death (DCD) setting. Successful transplant outcomes from uncontrolled DCD (uDCD) practices have been reported in multiple European programs. They utilize established protocols for uDCD procurement with normo-thermic or hypothermic regional perfusion to reduce ischemic damage. Further, manual or mechanical chest compressions using extrinsic devices, such as the LUCAS device, are implemented to maintain circulation before organ retrieval. Currently, uDCDs are not a major part of DCD organ utilization in the United States. We report our experience with utilization of kidneys from uDCD with the use of the LUCAS device without normothermic or hypothermic regional perfusion. We transplanted four kidneys from three uDCD donors without utilization of in situ regional perfusion and with prolonged relative warm ischemia time (rWIT) (>100min). All recipients had functional renal allografts and improved renal function after the transplant. To our knowledge, this is the 1st successful series reported in the United States of the utilization of kidneys from uDCDs without the utilization of in situ perfusion to maintain organ preservation with prolonged rWIT.

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.

Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69–1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205.

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.

MP31-11 DURATION OF THE AGONAL PHASE DOES NOT IMPACT DELAYED GRAFT FUNCTION NOR ONE-YEAR RENAL FUNCTION IN DONATION AFTER CIRCULATORY DEATH KIDNEY TRANSPLANTATION

You have accessJournal of UrologyCME1 Apr 2023MP31-11 DURATION OF THE AGONAL PHASE DOES NOT IMPACT DELAYED GRAFT FUNCTION NOR ONE-YEAR RENAL FUNCTION IN DONATION AFTER CIRCULATORY DEATH KIDNEY TRANSPLANTATION Yanbo Guo, Jirong Lu, Juliano Offerni, Danny Matti, Grant Luke, Edem Afenu, Alp Sener, and Patrick Luke Yanbo GuoYanbo Guo More articles by this author , Jirong LuJirong Lu More articles by this author , Juliano OfferniJuliano Offerni More articles by this author , Danny MattiDanny Matti More articles by this author , Grant LukeGrant Luke More articles by this author , Edem AfenuEdem Afenu More articles by this author , Alp SenerAlp Sener More articles by this author , and Patrick LukePatrick Luke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Donation after circulatory death (DCD) has significantly expanded the limited pool of available kidney allografts. The agonal phase is measured between the withdrawal of life-sustaining treatment and the time of circulatory arrest. Due to concerns about ischemic kidney injury during the agonal phase, many transplant programs use a cut-off time of 1 hour before abandoning the kidney retrieval. Our centre may use kidneys with an agonal phase for up to 3 hours. We evaluated how the length of the agonal phase influences graft outcomes. METHODS: We analysed a single-centre database of DCD renal transplant recipients between 2006-2020. Pediatric and donation after euthanasia donors were excluded. Data collected included recipient and donor demographics, surgery information, and outcomes up to one-year post transplant. SPSS was used for statistical analysis. RESULTS: Of the 182 DCD kidney donations that were identified, 27 (14.8%) arrested after 1 hour, and 10 (5.5%) arrested after 1.5 hours. The mean agonal time was 25 minutes. The longest interquartile range was between 37 and 130 minutes. Binary logistic regression showed no significant association between time to arrest and delayed graft function (DGF) (p=0.79) or primary nonfunction (PNF) (p=0.50). The Chi-square test also showed no significant association between DGF or PNF and donors who arrested in the longest quartile (X2=0.17, p=0.67), after 1 hour (X2=0.611, p=0.44), or after 1.5 hours (X2=0.161, p=0.69). Pearson correlation did show a weak association between time to arrest and a higher creatinine at three months (0.245, p=0.002) and six months (0.177, p=0.043), but this association was no longer present at one year (-0.032, p=0.77). CONCLUSIONS: We found no association between the length of the agonal phase and DGF or one-year renal function after transplantation. This supports the use of kidneys from DCD donors with agonal phases of one hour and beyond. Source of Funding: No disclosures © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e433 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yanbo Guo More articles by this author Jirong Lu More articles by this author Juliano Offerni More articles by this author Danny Matti More articles by this author Grant Luke More articles by this author Edem Afenu More articles by this author Alp Sener More articles by this author Patrick Luke More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

Role of post-transplant graft scintigraphy in kidney donation after circulatory death.

There is no consensus on how to predict post-transplant function of donation after circulatory death (DCD) kidneys. Thus, we aimed to identify renal scintigraphy parameters that could predict 1-year kidney function. In this single center study, we included all consecutive DCD kidney recipients between 2013 and 2021 (n = 29). Patients who did not have a scintigraphy within 10 days of transplantation (n = 3), recipients of multiple organs and less than 18 years old were excluded (n = 1). Primary endpoint was the estimated glomerular filtration rate (eGFR). Median eGFR and serum creatinine at 1 year were 67 µmol/L (56-81) and 111 ml/min (99-132), respectively. Among parameters tested, the 3rd/2nd-minute activity ratio had the best diagnostic performance (AUC: 0.74 and 0.71, for eGFR and creatinine) 1 year post transplantation. Using 1.21 as the best cut off, the 3rd/2nd-minute activity ratio specificity and sensitivity to predict eGFR >60 ml/min was 0.82 and 0.83. Renal function was significantly better at 1 week, 3, 6, and 12 months after transplantation in patients with 3rd/2nd-minute activity ratios above 1.21. This study suggests that the 3rd/2nd-minute activity ratio can predict graft function at 1 year. The benefit of post-transplant scintigraphy should be further validated in a prospective cohort.

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.

The development and outcomes of organ transplantation from donation after circulatory death in Taiwan

BackgroundIt is imperative to increase the donor pool due to a persistent shortfall of organs for transplantation. Therefore, organ donation after circulatory death (DCD) was reintroduced in Taiwan in 2017, and has become a rightful source for kidney and liver transplantation. We aim to report the preliminary outcomes of organ transplantation from DCD donors in Taiwan. MethodsAll data of 48 DCD donors and consecutively 106 grafts were obtained from the registry of Taiwan Organ Registry and Sharing Center. Kidney and liver transplantations were performed between Jan 5th, 2018 and Sep 24th, 2021. The primary endpoints were recipient survival and graft survival by using Kaplan-Meier method. ResultsOverall, DCD donors accounted for 9.6% (48/501) of all deceased donors in Taiwan from 2017 to 2021. The recipient survival for 3-month, 1-year, and 3-year were 99, 94, and 94% for DCD kidney transplants; 86, 76 and 76% for DCD liver transplants. The 3-month and three-year kidney graft survival (censored for death) reached 95% and 94%, respectively; while liver graft survival (censored for death) reached 95% and 89%, respectively. ConclusionsTransplantations from DCD donors showed satisfactory graft and recipient survivals in both kidney and liver transplants. Both kidney and liver transplantation from potential DCD donors should be advocated for its comparable outcomes to organs from brain-dead deceased donors.

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.

Organ donation after circulatory death as compared with organ donation after brain death in Switzerland - an observational study.

Organ donation after circulatory death (DCD) was reintroduced in Switzerland in 2011 and accounts for a third of deceased organ donors today. Controversy persists if DCD transplants are of similar quality to transplants following donation after brain death (DBD), mainly due to warm ischaemia time DCD organs are exposed to. We compared DCD with DBD in Switzerland. Data on deceased adults who were referred to and approved for organ donation from 1 September 2011 to 31 December 2019 were retrospectively analysed (217 DCD, 840 DBD donors). We compared DCD and DBD donor/organ characteristics, transplant rates of lungs, liver, kidneys, and pancreas, and early liver and kidney graft function in the recipient. The effect of DCD/DBD on transplant rates (organ transplanted or not) and 72-hour recipient graft function (moderate/good vs delayed graft function / organ loss) was analysed using multivariable logistic regression. Among utilised DCD donors, we analysed the effect of functional warm ischaemia time (FWIT) and donor age on 72-hour post-transplant liver and kidney graft function, also using multivariable logistic regression. DCD donors were more often male (64.5% vs 56.8% p = 0.039), presented with heart disease (36.4% vs 25.5%, p <0.001), were resuscitated before hospital admission (41.9% vs 30.7%, p = 0.006), and died from anoxia (41.9% vs 23.9%). Kidney function before transplantation was comparable, lung, liver and pancreas function were poorer in DCD than DBD. Eighty-one and 91% of approved DCD and DBD donors were utilised (p <0.001). Median FWIT in DCD was 29 minutes (interquartile range 25-35). DCD transplant rates ranged from 4% (pancreas) to 73% (left kidney) and were all lower compared with DBD. Seventy-two-hour liver graft function was comparable between DCD and DBD (94.2% vs 96.6% moderate/good, p = 0.199). DCD kidney transplants showed increased risk of delayed graft function or early organ loss (odds ratios 8.32 and 5.05; 95% confidence intervals CI 5.28-13.28 and 3.22-7.95; both p <0.001, for left and right kidney transplants, respectively). No negative effect of prolonged FWIT or higher donor age was detected. Despite less favourable donor/organ characteristics compared with donation after brain death, donation after circulatory death donors are increasingly referred and today provide an important source for scarce transplants in Switzerland. We identified a higher risk for delayed graft function or early organ loss for DCD kidney transplants, but not for DCD liver transplants. When carefully selected and allowed for other risk factors in organ allocation, prolonged functional warm ischaemia time or higher age in donation after circulatory death does not seem to be associated with impaired graft function early after transplantation.

Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion.

Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury.

Intraoperative Verapamil Fails to Reduce Delayed Graft Function in Donation After Circulatory Death Renal Allografts.

Background.The shortage of transplantable organs has led to increased utilization of kidneys that may be particularly vulnerable to ischemia-reperfusion injury (IRI) and delayed graft function (DGF). Kidneys from donation after circulatory death (DCD) donors have additional IRI from donor procurement that results in increased risk of DGF. Verapamil may reduce IRI in kidney allografts when given at the time of organ reperfusion. This study sought to determine if intraoperative administration of verapamil (Ver) could reduce the risk of DGF in DCD kidney transplants.Methods.A single-center retrospective matched cohort study was performed of 93 Ver (–) kidney transplant recipients compared with 93 Ver (+) kidney transplant recipients, matched by donor age, Kidney Donor Profile Index, and DCD status. Covariates that could impact DGF risk were evaluated by univariate and multivariate logistic regression analyses.Results.The Ver (–) and Ver (+) matched cohorts did not have any significant differences in the demographic covariates. There was no difference in DGF rate between the Ver cohorts in either the overall study population or within the DCD subgroup. There was a trend toward reduced DGF in the Ver (+) cohort for cold ischemia time (CIT) ≤24 h, but this failed to achieve statistical significance. On multivariate analysis, only CIT was found to be independently associated with DGF.Conclusions.Intraoperative verapamil failed to reduce DGF risk in DCD kidney allografts. Limitations to this study include nonrandomization for the intraoperative administration of verapamil and the mean CIT >24 h in the study population. Only CIT was an independent prognosticator for DGF on multivariate analysis in a cohort matched for DCD status, consistent with prior studies.