A new prediction model for acute kidney injury following liver transplantation using grafts from donors after cardiac death.

Acute kidney injury (AKI) is a major complication following liver transplantation (LT), which utilizes grafts from donors after cardiac death (DCD). We developed a machine-learning-based model to predict AKI, using data from 894 LT recipients (January 2015-March 2021), split into training and testing sets. Five machine learning algorithms were employed to construct the prediction models using 17 clinical variables. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. The best-performing model was further validated in an independent cohort of 195 LT recipients who received DCD grafts between April 2021 and December 2021. The Shapley additive explanations method was utilized to elucidate the predictions and identify the most crucial features. The gradient boosting machine (GBM) model demonstrated the highest AUC (0.76, 95% CI: 0.70-0.82), F1-score (0.73, 95% CI: 0.66-0.79) and sensitivity (0.74, 95% CI: 0.66-0.80) in the testing set and a comparable AUC (0.75, 95% CI: 0.67-0.81) in the validation set. The GBM model identified high preoperative indirect bilirubin, low intraoperative urine output, prolonged anesthesia duration, low preoperative platelet count and graft steatosis graded NASH Clinical Research Network 1 and above as the top five important features for predicting AKI following LT using DCD grafts. The GBM model is a reliable and interpretable tool for predicting AKI in recipients of LT using DCD grafts. This model can assist clinicians in identifying patients at high risk and providing timely interventions to prevent or mitigate AKI.

National survey on deceased donor organ transplantation during the COVID-19 pandemic in Japan.

PURPOSE: We investigated the status of deceased organ donation and transplantation through a questionnaire distributed to transplant centers in Japan during the COVID-19 pandemic. METHODS: The questionnaire was distributed electronically to 206 transplant centers for heart (n = 11), lung (n = 10), liver (n = 25), kidney (n = 130), pancreas (n = 18), and small intestine (n = 12) transplantation. Organ donations and organ transplantation data were extracted from the Japan Organ Transplant Network website. RESULTS: We received questionnaire responses from 177 centers (response rate, 86%). In 2020, the number of brain-dead donors (BDDs) decreased to 68 (69% of the year-on-year average) and the number of donors after cardiac death (DCDs) decreased to 9 (32% of the year-on-year average). Eighty-five (48%) transplant centers (heart, n = 0; lung, n = 0; liver, n = 4; kidney, n = 78; pancreas, n = 22; and small intestine, n = 0) suspended transplant surgeries in response to the COVID-19 pandemic. Consequently, the number of organ transplantations from deceased donors was significantly lower in 2020 than in 2019. CONCLUSION: Although the COVID-19 pandemic has had less impact in Japan than in other countries, it has affected transplantation activity significantly, suspending transplantation surgeries in 48% of the transplantation centers, including 78% of the kidney transplantation centers, and reducing the number of organ donations to 61% of the year-on-year average.

Pharmacological Activating Transcription Factor 6 Activation Is Beneficial for Liver Retrieval With ex vivo Normothermic Mechanical Perfusion From Cardiac Dead Donor Rats.

Background: Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval. Methods: The livers from DCD rats were exposed to 30 min of warm ischemia and 8 h cold preservation followed by 2 h NMP with or without an ATF6 activator in the perfusate. Perfusates and livers were harvested to detect ATF6 expression, liver function, and inflammation. Results: DCD livers with NMP were associated with ATF6 overexpression and activation based on IHC and WB (P < 0.05). The ATF6 activator downregulated perfusate aminotransferases, decreased the Suzuki score, downregulated CD68 and MPO based on IHC, induced the expression of cytochrome c in mitochondria and inhibited the expression of cytochrome c in cytoplasm based on WB, reduced TNFα and IL-6 levels based on ELISA, decreased levels of MDA, GSSG and ATP, and increased SOD activity and GSH levels in the perfused livers (P < 0.05). Conclusion: ATF6 is important for liver retrieval, and an exogenous ATF6 activator accelerates liver retrieval from DCD rats in an ex vivo NMP model.

Extended criteria grafts and emerging therapeutics strategy in liver transplantation. The unstable balance between damage and repair.

Due to increasing demand for donor organs, "extended criteria" donors are increasingly considered for liver transplantation, including elderly donors and donors after cardiac death. The grafts of this subgroup of donors share a major risk to develop significant features of ischemia reperfusion injury, that may eventually lead to graft failure. Ex-situ machine perfusion technology has gained much interest in liver transplantation, because represents both a useful tool for improving graft quality before transplantation and a platform for the delivery of therapeutics directly to the organ. In this review, we survey ongoing clinical evidences supporting the use of elderly and DCD donors in liver transplantation, and the underlying mechanistic aspects of liver aging and ischemia reperfusion injury that influence graft quality and transplant outcome. Finally, we highlight evidences in the field of new therapeutics to test in MP in the context of recent findings of basic and translational research.

An Update on Usage of High-Risk Donors in Liver Transplantation.

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

A single center study of risk factors on short term prognosis after kidney transplantation from donors after cardiac death / 中华泌尿外科杂志

Objective To discuss the risk factors on short-term prognosis after kidney transplantation from donors after cardiac death (DCD). Methods We retrospectively analyzed the information of donors and recipients who performed DCD donor kidney transplantation in our center between January 2011 and August 2015, including 64 donors and 95 recipients. Also, we analyzed the potential relationship among donors' clinical characteristics and the early recovery of graft function, including the incidence of delayed graft function(DGF)and the serum creatinine (SCr) on the 90th day, and infection rate after kidney transplantation.Results We found that when donors had the factors of WIT>10 min, urine volume<100 ml/h, SBP≤100 mmHg or a history of CPR, the incidence of recipients' DGF were 55.6%,73.3%,62.5%,77.8% respectively with a significant difference. Recipients would have more chance to be infected if donors have the following characteristics: male, older than 50 years, died of cerebral hemorrhage which was caused by cardiovascular diseases, WIT>30 min, treated in ICU for more than 10 days or infection. Conclusions Nowadays, DCD has become the main graft source in Chinese kidney transplantation. This research indicates that the donors' factors may affect the recovery of graft function and the incidence of infection after kidney transplantation to some extent.By evaluating rigorously and preserving quality of renal grafts carefully, DCD would become more safe and valid.

An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI.

Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.

Influence of extracorporeal membranous oxygenation on small bowel preservation in a porcine model of controlled donors after cardiac death / 中华器官移植杂志

Objective To evaluate the effect of extracorporeal membranous oxygenation (ECMO) on the small bowel preservation in a porcine model of controlled donors after cardiac death (CDCD).Method The domestic crossbred donor pigs were anesthetized and ventilated with 100％ oxyger.An intravenous cannula was placed through iliac arteries and jugular vein,and connected to ECMO system.The ECMO was performed to infuse abdominal organs when cardiac death was declared.Pathology,electron microscope,energy metabolism and cell apoptosis level of intestinal mucosa were evaluated before operation,in cardiac death and at the end of extracorporeal support,respectively.Result The normothermic extracorporeal support could quickly restore graft blood supply and oxygenation.One-h extracorporeal support could improve the energy status in intestine of donation after cardiac death (DCD).The histologic damage and apoptosis of 1-h extracorporeal support had no significant difference with those before operation and in cardiac death (P＞0.05).With the extension of extracorporeal support,the intestinal mucosa damage degree was gradually increased,and the content of adenosine triphosphate in intestinal mucosa reduced gradually.Conclusion The normothermic extracorporeal support for 1 h in DCD is beneficial for improving the viability of small bowel.However,the integrity of intestinal mucosa is destroyed gradually as extracorporeal supporting time over,which may be initiated by the activation of intestinal epithelial apoptosis.

Trends in deceased organ donation and utilization in Korea: 2000-2009.

Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (> or = 50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD.

Trends in Deceased Organ Donation and Utilization in Korea: 2000-2009

Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (> or =50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD.