Donation After Brain Death Grafts Research Articles

Hepatitis C-positive grafts for hepatitis C-negative recipients in liver transplantation: Buried treasure or depleting resource?

Long-term outcomes of using hepatitis C virus (HCV) positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival (GS). The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death (DCD) donors were seldom utilized in the study period. The 5-year GS rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD (p=0.56) or DCD (p=0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year GS to non-fibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or DCD grafts for HCV-negative recipients is comparable to that of other graft types, and that fibrotic grafts have the potential to expand the DBD donor pool.

Kidney Transplant Outcome Following Donation After Euthanasia

In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool. To investigate the outcomes of DCD-V kidney transplantation and compare them with outcomes of kidney transplantation after circulatory death after withdrawal of life-sustaining therapies (DCD type III [DCD-III]) and donation after brain death (DBD). A retrospective cohort study was conducted using the database from the Dutch Transplant Foundation. All kidney transplants in the Netherlands between January 2012 (start of the euthanasia program) and July 2023 were included. Follow-up was obtained through 5 years after transplantation. Data analysis was performed from November 2023 until February 2024. Kidney transplantation with a DCD-V graft compared with DCD-III and DBD grafts. The primary outcome was death-censored graft survival until 5 years after transplantation. Secondary outcomes were the incidence of delayed graft function (DGF), permanent nonfunction (PNF), serum creatinine concentration, and patient survival until 5 years after kidney transplantation. A total of 145 DCD-V kidney transplants were compared with 1936 DCD-III and 1255 DBD kidney transplants. Median (IQR) recipient age was 59 (46-66) years in the DCD-V cohort, compared with 61 (50-68) years in the DCD-III cohort and 61 (50-68) years in the DBD cohort. The incidence of DGF with DCD-V kidney transplants (26%) was significantly less than that with DCD-III kidney transplants (49%; P < .001) and similar to that with DBD kidney transplants (22%; P = .46). PNF occurrence with DCD-V kidneys (6%) was similar to that with DCD-III kidneys (6%; P = .79) and higher than in DBD kidneys (4%; P < .001). There was no difference in 5-year death-censored graft survival between DCD-V grafts (82%) and DCD-III (86%; P = .99) or DBD (84%; P = .99) grafts. There was no difference in 5-year patient survival between DCD-V kidney transplants (69%) and DCD-III (76%; P = .45) or DBD (73%; P = .74) kidney transplants. A propensity score analysis was performed to match the DCD-V and DCD-III cohort, showing results similar to those of the unmatched cohort. This study found that DCD-V kidney transplantation yielded a lower incidence of DGF compared with DCD-III kidney transplantation and yielded long-term results similar to those of DCD-III and DBD kidney transplantation. The findings suggest that DCD-V is a safe and valuable way to increase the kidney donor pool.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Comparison of Kidney Graft Function and Survival in an Emulated Trial With Living Donors and Brain-Dead Donors.

Living donation (LD) transplantation is the preferred treatment for kidney failure as compared to donation after brain death (DBD), but age may play a role. We compared the 1-year estimated glomerular filtration rate (eGFR) after kidney transplantation for recipients of LD and DBD stratified by recipient and donor age between 2015 and 2018 in a matched cohort. The strength of the association between donation type and 1-year eGFR differed by recipient age (P interaction < 0.0001). For LD recipients aged 40-54years versus same-aged DBD recipients, the adjusted odds ratio (aOR) for eGFR ≥60mL/min/1.73m2 was 1.48 (95% CI: 1.16-1.90). For DBD recipients aged ≥ 60years, the aOR was 0.18 (95% CI: 0.12-0.29) versus DBD recipients aged 40-54years but was 0.91 (95% CI: 0.67-1.24) versus LD recipients aged ≥60years. In the matched cohort, 4-year graft and patient survival differed by donor age and type. As compared with DBD grafts, LD grafts increased the proportion of recipients with 1-year eGFR ≥60mL/min/1.73m2. Recipients aged ≥60years benefited most from LD transplantation, even if the donor was aged ≥60years. For younger recipients, large age differences between donor and recipient could also be addressed with a paired exchange program.

Should advanced donor age be a deterrent in the utilization of grafts from donation after cardiac death in deceased donor liver transplantation? The Toronto experience.

Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

Donation after Circulatory Death Grafts Have Comparable Outcomes to Donation after Brain Death Grafts in Liver Transplantation

Introduction: In the United States, 30% of donation after circulatory death (DCD) grafts are discarded for liver transplantation (LT). DCD grafts can mitigate liver organ shortage but is underused due to the believe of poor outcomes in graft and patient survival. Recent studies have shown comparable outcomes to donation after brain death (DBD). The aim of this study is to review our experience with the use of DCD grafts. Methods: Retrospective single center study, whole grafts transplanted between January 2014 and December 2021 were included. Propensity score match was done using recipient age, recipient gender, MELD score, wait time, number of previous LT, cold ischemia time, year of LT and surgeon as cofounders. Multivariate Cox-regression models were created with significant variables in the univariate analysis. Finally, Kaplan-Meier curves with log-rank test were performed. Results: A total of 63 DCD and 148 DBD grafts were included. The patients were predominantly males (59.2%), median age was 58 (IQR 49-65), the most common reason for transplantation was alcoholic cirrhosis (20.4%) and were listed for their first LT (95.7%). Number of transplants (HR:15.39, 95%CI: 3.56-66.49, p < 0.001) and BMI (HR:1.1, 95%CI: 1.01-1.2, p = 0.03) were associated to graft loss. DCD was not associated with graft (HR:0.47, 95%CI: 0.14-1.58, p = 0.2) or patient (HR:0.33, 95%CI: 0.08-1.42, p = 0.1) survival. Graft (92.9% DBD vs 96.8% DCD, p = 0.2) and patient (93.6% DBD vs 100% DCD, p = 0.1) 2-year survival were similar. Conclusion: When matching different cofounders, the use of DCD grafts has comparable outcomes to those DBD grafts.

Postreperfusion syndrome in liver transplantation: Outcomes, predictors, and application for recipient selection.

This study aimed to identify risk factors for postreperfusion syndrome (PRS) and its impact on LT outcomes. Data analysis was performed in 1021 adult patients undergoing donation after brain death (DBD) LT to identify PRS incidence, the risk factors for PRS development, and its impact on LT outcomes. The overall incidence of PRS was 16.1%. Independent risk factors for PRS included donor age (odds ratio (OR) 1.01, P=.02), donor body mass index (BMI) (OR 1.04, P=.003), moderate macrosteatosis (OR 2.48, P=.02), and cold ischemia time (CIT) (OR 1.06, P=.02). On multivariable analysis for 30-day graft failure, PRS (hazard ratio (HR) 3.49; P<.001) and Model for End-stage Liver Disease (MELD) score (HR 1.01; P=.05) were independent risk factors. Patients were categorized into four distinct groups based on PRS risk groups and MELD groups, which showed different 1-year graft survival (P<.001). There were comparable outcomes between low PRS risk- high MELD and high PRS risk - low MELD group (P=.33). Donor age, donor BMI, moderate macrosteatosis, and CIT were identified as risk factors for the development of PRS in LT using DBD grafts. PRS risk evaluation may improve donor-to-recipient matching based on their MELD scores.

Long-term outcomes of transplant kidneys donated after circulatory death.

Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years. This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts.

Early Allograft Dysfunction After Liver Transplantation With Donation After Circulatory Death and Brain Death Grafts: Does the Donor Type Matter?

Background.Early allograft dysfunction (EAD) after liver transplantation has been associated with long-term reduced graft and patient survival.Methods.In this single-center cohort study, we aimed to compare incidence, risk factors, and outcomes in liver transplant recipients who developed EAD. Patients who received donation after circulatory death (DCD) or donation after brain death (DBD) grafts between January 2007 and December 2017 were included. EAD was defined as bilirubin of ≥10 mg/dL (171 μmol/L) or an international normalized ratio of ≥1.6 on postoperative day 7 or transaminases >2000 U\\L in the first-week posttransplantation as previously described.Results.In our cohort of 1068 patients, incidence of EAD was 44%. EAD occurred more frequently in the DCD versus DBD group (71% versus 41%, P < 0.01). Overall, recipients who developed EAD showed a significantly lower graft and patient survival at 1, 3, and 5 y after transplantation (all P < 0.05). This was also the case for recipients of DBD grafts. However, for recipients of DCD grafts, patient and graft survival were not affected by the presence of EAD. For recipients of DBD grafts, donor age, body mass index (BMI) and gender, recipient BMI and model for end-stage liver disease score and warm and cold ischemia time were associated with EAD. For DCD recipients, donor BMI and cold ischemia time were associated with EAD.Conclusions.In our cohort study, EAD resulted in reduced long-term patient and graft survival only for DBD recipients but not for DCD recipients. Predictive markers for EAD were dependent on the donor type.

Clinical and Functional Outcomes after Lung Transplantation with Grafts from Donation after Circulatory (DCD) Donors. Preliminary Results of a Clinical Trial

<h3>Purpose</h3> We present the results of a clinical trial (NCT02061462) comparing outcomes after lung transplantation (LT) of subjects receiving lungs from donation after brain death (DBD) donors with that of subjects receiving lungs from donation after circulatory death (DCD) donors, procured using our original open lung strategy. Briefly, our protocol consists of a non-rapid normothermic open-lung procurement using recruitment manoeuvres, protective ventilation and CPAP without topical cooling. <h3>Methods</h3> We evaluated patients undergoing bilateral LT from 11/2014 to 07/2019; exclusion criteria: recipients ≤14 years, re-LT, donors ≥65 years, DCD category I and IV. Variables were prospectively recorded as well as respiratory functional parameters in the first year. <h3>Results</h3> We performed 143 LT; 22 cases were excluded, 121 were enrolled: 11 recipients received lungs from DCD donors (5 and 6 from DCD category II and III, respectively). The two groups had similar features. Most of the subjects had cystic fibrosis (72,7% and 61,9% of DCD and DBD, respectively). DCD donors' BMI was significantly higher (p=0.022); 15,5% of DBD grafts underwent machine perfusion. Duration of postoperative mechanical ventilation was higher in the DCD group (DCD vs DBD=2 vs 1 day, p=0.011). Incidence of grade 3 primary graft dysfunction was 27,3% in the DCD group and 18,2% in the DBD group (p=0.742). Cold ischemia and preservation times were significantly higher in the DCD group (p<0.001). Airway complications occurred in 18,2% and 6,4% in DCD and DBD recipients, respectively (Table 1). Mean FEV1 was significantly higher in the DBD group at 6 months (83,5% vs 78,5%) but not at 1 year (86,0% vs 81,7%). FVC and Tiffenau did not significantly differ. <h3>Conclusion</h3> Regardless of the small study population, our results are encouraging. Our data show the feasibility of LT from DCD donors using our original protocol, with adequate grafts function and survival.

FGF15 improves outcomes after brain dead donor liver transplantation with steatotic and non-steatotic grafts in rats

Donation after brain death (DBD) grafts are associated with reduced graft quality and function post liver transplantation (LT). We aimed to elucidate i) the impact of FGF15 levels on DBD grafts; ii) whether this impact resulted from altered intestinal FXR-FGF15; iii) whether administration of FGF15 to donors after brain death could confer a benefit on graft function post LT; and iv) whether FGF15 affects bile acid (BA) accumulation. Steatotic and non-steatotic grafts from DBD donors and donors without brain death were transplanted in rats. FGF15 was administered alone or combined with either a BA (cholic acid) or a YAP inhibitor. Brain death induced intestinal damage and downregulation of FXR. The resulting reduced intestinal FGF15 was associated with low hepatic FGF15 levels, liver damage and regenerative failure. Hepatic FGFR4-Klb - the receptor for FGF15 - was downregulated whereas CYP7A1 was overexpressed, resulting in BA accumulation. FGF15 administration to DBD donors increased hepatic FGFR4-Klb, reduced CYP7A1 and normalized BA levels. The benefit of FGF15 on liver damage was reversed by cholic acid, whereas its positive effect on regeneration was maintained. YAP signaling in DBD donors was activated after FGF15 treatment. When a YAP inhibitor was administered, thebenefits of FGF15 on regeneration were abolished, whereas itspositive effect on hepatic damage remained. Neither the Hippo-YAP-BA nor the BA-IQGAP1-YAP axis was involved in the benefits of FGF15. Alterations in the gut-liver axis contribute to the reduced quality of DBD grafts and the associated pathophysiology of LT. FGF15 pre-treatment in DBD donors protected against damage and promoted cell proliferation. After brain death, potential liver donors have reduced intestinal FXR, which is associated with reduced intestinal, circulatory and hepatic levels of FGF15. A similar reduction in the cell-surface receptor complex Fgfr4/Klb is observed, whereas CYP7A1 is overexpressed; together, these molecular events result in the dangerous accumulation of bile acids, leading to damage and regenerative failure in brain dead donor grafts. Herein, we demonstrate that when such donors receive appropriate doses of FGF15, CYP7A1 levels and hepatic bile acid toxicity are reduced, and liver regeneration is promoted.

Results in liver transplantation using grafts from donors after controlled circulatory death: A single-center experience comparing donor grafts harvested after controlled circulatory death to those harvested after brain death.

In recent years, interest in donation after cardiac death (DCD) has increased. Although DCD liver transplantation (LT) has demonstrated satisfactory long-term outcomes, different studies have shown poorer patient and graft survival after DCD than after donation after brain death (DBD). This study aimed to evaluate the results of LT using controlled DCD (cDCD) donors, specifically the incidence of primary non-function and ischemic cholangiopathy (IC), and to compare these results with those of LT using DBD in the same time period. Between June 2012 and July 2018, we performed 66 transplants using cDCD and 258 with DBD grafts. The incidence of IC was similar in both groups (2% in DBD, 1.5% in DCD; P=.999). No significant differences were found for overall graft and patient survival rates between the groups at 1 and 2years post-transplantation. This study provided evidence that cDCD donors exhibit excellent graft and patient survival outcomes. When the warm ischemia time is <30minutes and cold ischemia time is <6hours, the graft and patient survival rates and the incidence of IC in DCD are similar to those in DBD, even when using donors without age restrictions.

Cell-free MicroRNA miR-505-3p in Graft Preservation Fluid Is an Independent Predictor of Delayed Graft Function After Kidney Transplantation.

Delayed graft function (DGF), a common complication after transplantation of deceased donor kidneys, affects both short- and long-term outcomes. Currently available biomarkers during graft preservation lack sensitivity in predicting risk for DGF. The aim of this study is to identify cell-free micro ribonucleic acid (miRNA) biomarkers in graft preservation fluid predictive of DGF after kidney transplantation. Vascular bed preservation fluid was collected from 48 kidney grafts from donation after circulatory death (DCD) or donation after brain death (DBD) donors. miRNA profiles were determined by polymerase chain reaction (PCR) array (n = 8) and validated by reverse transcription and quantitative PCR (n = 40). Graft function posttransplantation was defined as immediate good function (IF) or DGF. A total of 223 miRNAs fulfilled the preset parameters (Ct < 40 in 3 or more samples) and were included in the analysis. Thirty-two miRNAs were significantly different between DGF and IF kidney grafts (P < 0.05) but, after correction for multiple testing, only miR-505-3p remained significant. The significant association of high miR-505-3p levels with DGF was confirmed in an independent validation cohort using conventional reverse transcription and quantitative PCR detection. Multivariate analyses showed miR-505-3p as an independent predictor for DGF (odds ratio, 1.12; P = 0.028). If stratified for donor type, miR-505-3p levels remained significantly different between IF and DGF in DCD grafts (P < 0.01), but not in DBD grafts. Receiver operating characteristic curve analysis showed a high sensitivity and specificity (area under the curve, 0.833). In DCD grafts, high levels of miR-505-3p in preservation fluid are associated with increased risk of DGF after kidney transplantation. Further study is required to confirm the utility of cell-free miR-505-3p as prognostic biomarker for DGF.

Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts.

Hepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers. A total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT. Hepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P=0.04) and had worse primary patency rates (logrank, P=0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts. We observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.

The evolution of donation after circulatory death renal transplantation: a decade of experience

This study compared long-term outcomes of renal transplantation from donors following donation after circulatory death (DCD) with those following donation after brain death (DBD) from one of the largest centres in the UK. Recipients of renal transplants from deceased donors between 2002 and 2014 were identified from a prospectively maintained database. Outcomes were compared between DCD (468) and DBD (905) donors and between standard criteria donors (SCDs) and extended criteria donors (ECDs). Graft survival (GS) and patient survival (PS) from DCD and DBD donors were comparable up to 10 years (GS: 61 versus 55%, P = 0.780; PS: 78 versus 71%, P = 0.285, respectively). Graft function was comparable after 3 months. GS and function were worse in the ECD groups, with no difference between EC-DBD and EC-DCD. PS in the ECD groups was worse than the SCD groups and PS in the EC-DCD group was worse than in the EC-DBD group. DCD donors were an independent risk factor for delayed graft function. Post-operative complications and EC-DCD donation were independent risk factors for reduced GS and PS. This study supports the use of DCD renal grafts with comparable long-term survival and function to DBD grafts. The use of EC-DCD grafts is justified in selected recipients and provides acceptable function and survival advantages over dialysis.

Outcomes of Liver Transplantation Using Organ Donation After Brain Death (DBD) versus Organ Donation After Cardiac Death (DCD): A Single Center Experience

Introduction: Donation after cardiac death (DCD) liver allografts have been associated with primary nonfunction, ischemic cholangiopathy, hepatic artery stenosis and a higher re-transplantation rate when compared with donation after brain death (DBD) allografts. The number of liver transplantation (LT) with DCD allografts has increased in the recent years. We present our experience with using this extended criteria donor grafts. Primary objective: To compare patient and graft survival between DBD and DCD allografts. Secondary objective: To compare biliary and vascular rates of LT complications between both groups. Methods: We retrospectively reviewed all LTs performed at a major transplant center from January 2012 to April 2017. We included patients who received a combined liver and kidney transplant (n = 29), and excluded patients who received a split LT (n =4). DCD and DBD allografts were compared using Chisquare, Fischer exact test, log-rank tests and Kaplan-Meier plot analysis. Results: A total of 409 patients were analyzed, 100 patients received DCD grafts, and 309 patients received DBD grafts. There was no significant difference in the recipient age, gender, BMI or donor age, gender and BMI of both groups. The DBD recipients had a higher biological (p = 0.001) and match MELD scores, (p = 0.005) while the DCD donors had a higher donor risk index (p < 0.0001). Cholangiopathy in the DCD group was 12.2% and 3.6% in the DBD group, p = 0.001. Although, the rate of non-anastomotic biliary strictures, however, was significantly different between both groups (Table 1), cholangiopathy did not appear to be significant in predicting patient or graft survival in a sub-group analysis. Patient survival in DCD recipients was 92.7% at 1 year, and 80.3% at 4 years versus 96% at 1 year and 88.5% at 4 years in DBD recipients, p = 0.27. Graft survival in DCD recipients was 88% at 1 year, and 76.3% at 4 years versus 94.1% at 1 year and 78.8% at 4 years in DBD recipients, p = 0.34 (Figure 1).Figure: Patient and graft survival Kaplan-Meier curves.Conclusion: With careful selection, LT outcomes of DCD organs are comparable to DBD organs.Figure: Demographics and outcomes by donor relationship.

Long-term results after transplantation of pediatric liver grafts from donation after circulatory death donors.

BackgroundLiver grafts from donation after circulatory death (DCD) donors are increasingly accepted as an extension of the organ pool for transplantation. There is little data on the outcome of liver transplantation with DCD grafts from a pediatric donor. The objective of this study was to assess the outcome of liver transplantation with pediatric DCD grafts and to compare this with the outcome after transplantation of livers from pediatric donation after brain death (DBD) donors.MethodAll transplantations performed with a liver from a pediatric donor (≤16 years) in the Netherlands between 2002 and 2015 were included. Patient survival, graft survival, and complication rates were compared between DCD and DBD liver transplantation.ResultsIn total, 74 liver transplantations with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The median donor warm ischemia time (DWIT) was 24 min (range 15–43 min). Patient survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have been rejected for transplantation when the DWIT ≥30 min (n = 4), the 10-year graft survival rate would have been 81% after DCD transplantation. The rate of non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00). Other complication rates were also similar between both groups.ConclusionsTransplantation of livers from pediatric DCD donors results in good long-term outcome especially when the DWIT is kept ≤30 min. Patient and graft survival rates are not significantly different between recipients of a pediatric DCD or DBD liver. Moreover, the incidence of non-anastomotic biliary strictures after transplantation of pediatric DCD livers is remarkably low.

Inflammatory genes in rat livers from cardiac- and brain death donors

BackgroundLiver transplantation (LT) is the only life-saving treatment for patients with end-stage liver disease. The increase in patients has prompted the use of not only donation after brain death (DBD) donors but also living donors (LD) and donation after cardiac death (DCD) donors. Donor-type affects early graft function and graft survival as evidenced by an increased risk of developing ischemic type biliary lesions and higher risk of graft loss in DCD as compared with those in DBD grafts. MethodsUsing a rat model, we used quantitative reverse transcription-polymerase chain reaction to examine expression levels of proinflammatory, cytoprotective, and injury genes and determined apoptosis in DCD and DBD livers at different time points after retrieval. ResultsAfter retrieval, early mediators of inflammation MCP-1, HMGB1, and toll-like receptor (TLR 4) were increased in DCD livers, whereas the proinflammatory genes interleukin 6, interleukin 1β, tumor necrosis factor alpha, P-selectin, and E-selectin were massively upregulated in DBD compared with those in LD livers. HO-1 was increased in both postmortem groups. After cold ischemia, DCD livers showed increased levels of MCP-1, TLR4, and HMGB1, whereas expression of proinflammatory genes in DBD liver remained high. During 12 h of cold storage, expression levels remained stable except Hif-1α and HMGB1. DCD showed higher number of apoptotic cells compared with DBD livers. ConclusionsCompared with LD, DCD livers showed only mild upregulation of inflammatory markers, but increased levels of MCP-1, HMGB1, and TLR4, and more apoptotic cells. In contrast, DBD livers showed a massive inflammatory response. These differences in tissue injury and inflammatory response might be relevant for the outcome after LT.

Perioperative complications in liver transplantation using donation after cardiac death grafts: A propensity-matched study

Donation after cardiac death (DCD) is an important source for expanding the donor pool for liver transplantation (LT). Although the long-term outcomes of LT using DCD grafts have been extensively studied, perioperative complications related to DCD grafts are rarely reported. The aim of this study was to determine whether DCD grafts were associated with a higher incidence of postreperfusion complications and worse outcomes in adult LT patients. After institutional review board approval, the medical records of all adult patients who underwent LT at our medical center between 2004 and 2011 were reviewed. Postreperfusion complications and posttransplant outcomes were compared between patients receiving DCD grafts and patients receiving donation after brain death (DBD) grafts. In all, 74 patients received DCD grafts during the study period, and 1369 patients received DBD grafts. An initial comparison showed that many preoperative, prereperfusion, and donor variables in the DCD group differed significantly from those in the DBD group. Propensity matching was chosen so that adjustments could be made for the differences. A postmatching analysis showed that the preoperative, prereperfusion, and donor variables no longer differed between the 2 groups. The postreperfusion requirements for blood products and vasopressors, the posttransplant ventilation times, the incidence of posttransplant acute renal injury, and the 30-day and 1-year patient and graft survival rates were comparable between the 2 groups. However, patients receiving DCD grafts experienced significantly higher rates of hyperkalemia (33.8% versus 18.9%, P < 0.05) and postreperfusion syndrome (PRS; 25.7% versus 12.3%, P < 0.05). In conclusion, after adjustments for preoperative and prereperfusion risks via propensity matching, DCD grafts remained a risk factor for postreperfusion hyperkalemia and PRS. A prophylactic regimen aimed at decreasing postreperfusion hyperkalemia and PRS is recommended for the management of LT using DCD grafts.