Development status and new challenges of heart transplantation / 器官移植

Heart transplantation is the primary therapeutic option for patients with end-stage heart failure. The shortage of donors has been the main limiting factor for the increasing quantity of heart transplantation. With persistent updating and introduction of novel technologies, the donor pool has been increasingly expanded, such as using the heart from older donors, donors infected with hepatitis C virus, donors dying from drug overdose or donation after cardiac death (DCD) donors, etc. Meantime, the proportion of recipients with advanced age, multiple organ dysfunction, mechanical circulatory support and human leukocyte antigen antibody sensitization has been significantly increased in recent years. The shortage of donors, complication of recipients' conditions, individualized management of immunosuppressive therapy and prevention and treatment of long-term cardiac allograft vasculopathy are all challenges in the field of heart transplantation. In this article, novel progresses on donor pool expansion, improving the quality of recipients, strengthening the diagnosis and treatment of rejection, and preventing cardiac allograft vasculopathy were reviewed, aiming to prolong the survival and enhance the quality of life of patients with end-stage heart failure on the waiting list or underwent heart transplantation.

Research status of machine perfusion of heart / 器官移植

High-quality donor heart is the prerequisite and fundamental guarantee for successful heart transplantation. Reasonable donor heart preservation technique plays a key role in improving the quality of donor heart and the prognosis of heart transplantation. Static cold storage (SCS) is currently the standard preservation technique for cardiac allograft. However, it is prone to cause severe cold ischemia injury to the donor heart, and it is impossible to evaluate heart function during SCS. As an important emerging technique of organ preservation, machine perfusion better matches with physiological conditions compared with SCS, which may remove metabolic wastes and provide basic substances for metabolic needs during organ preservation, prolong the preservation time and improve the preservation effect to a certain extent. Besides, it may also effectively evaluate organ function and improve clinical prognosis of heart transplantation. Meantime, it can also repair organ damage, significantly optimize organ quality and improve the utilization rate of donor organs. In this article, research status of machine perfusion of donor heart was reviewed.

Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3 / 器官移植

Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.

Liver transplantation for acute liver failure in children: 8-year experience in a single center / 器官移植

Objective To evaluate the efficacy of liver transplantation for acute liver failure (ALF) in children. Methods Clinical data of 15 children with ALF who underwent liver transplantation were collected and retrospectively analyzed. The proportion of ALF among children undergoing liver transplantation during the same period was calculated. The characteristics, postoperative complications and clinical prognosis of ALF children receiving liver transplantation were analyzed. Results In the same period, the proportion of ALF was 2.0% (15/743) among pediatric recipients undergoing liver transplantation. All 15 children had acute onset of ALF, and most of them were accompanied by fever, diarrhea and progressive yellowing of skin and sclera. Thirteen children were complicated with hepatic encephalopathy before operation (6 cases of stage Ⅳ hepatic encephalopathy), and two children were complicated with myelosuppression and granulocytopenia before liver transplantation. Ten children underwent living donor liver transplantation with relative donor liver, 4 received liver transplantation from donation after cardiac death (DCD), and 1 underwent Domino donor-auxiliary liver transplantation. Of 15 children, 12 recipients had the same blood type with their donors, 1 recipient had compatible blood type with the donor and 2 cases had different blood type with their donors. Among 15 children, 10 cases developed postoperative complications. Postoperative cerebral edema occurred in 5 cases, of whom 4 cases died of diffuse cerebral edema, and the remaining case was in a persistent vegetative state (eyes-open coma). Postoperative cytomegalovirus (CMV) infection was seen in 5 cases. Two children presented with aplastic anemia and survived after bone marrow transplantation, 1 case died of CMV hepatitis and viral encephalitis, and 2 cases died of diffuse brain edema. One child developed graft-versus-host disease (GVHD) after liver transplantation, and died of septic shock after bone marrow transplantation. Nine children survived and obtained favorable liver function during postoperative follow-up. Conclusions Liver transplantation is an efficacious treatment for ALF in children, which may enhance the survival rate. Brain edema is the main cause of death in ALF children following liver transplantation, and treatment such as lowering intracranial pressure, improving brain metabolism and blood purification should be actively performed. Liver transplantation should be promptly performed prior to the incidence of irreversible neurological damage in ALF children, which might prolong the survival and enhance long-term prognosis.

Research progress on the role of oxidative stress in ischemia-reperfusion injury of marginal donor liver transplantation / 器官移植

Common marginal donor liver mainly consists of fatty donor liver, elderly donor liver, small volume donor liver and liver graft from donation after cardiac death (DCD), etc. The application of marginal donor liver may resolve the severe shortage of donor liver to certain extent. Nevertheless, marginal donor liver yields a higher risk of ischemia-reperfusion injury (IRI) and causes more severe IRI than normal donor liver, which is a main cause for the failure of transplantation. In addition, oxidative stress is a major risk factor causing IRI of marginal donor liver. Therefore, how to mitigate oxidative stress and alleviate IRI of marginal donor liver has become a hot spot in clinical practice. Reactive oxygen species (ROS)-mediated oxidative stress occurs throughout the whole process of IRI. In this article, the role of oxidative stress in IRI of marginal donor liver transplantation and the ROS-targeted prevention and treatment were reviewed, aiming to provide reference for clinical practice.

Current status and prospect of global development of lung transplantation / 器官移植

During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.

Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation / 器官移植

Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.

Experimental study on the role of IL-10 in improving donor lung function after ex vivo lung perfusion in rats of cardiac death / 器官移植

Objective To evaluate the effect of interleukin (IL)-10 on donor lung function after ex vivo lung perfusion (EVLP) in rats of cardiac death. Methods Twenty adult male SD rats were randomly divided into the simple perfusion group (group A, n=10) and modified perfusion group (group B, n=10). Perfusate A (without IL-10) and perfusate B (supplemented with IL-10) was administered in group A and B, respectively. The EVLP rat models of cardiac death were established. The appearance of donor lung, dry-to-wet (D/W) ratio of donor lung tissues, the function and metabolism of donor lung, the morphology of donor lung and the levels of inflammatory markers of donor lung were statistically compared between two groups. Results After perfusion, evident edema of the whole donor lung, poor compliance and a large amount of edema fluid discharged from the airway were observed in group A, whereas no obvious edema and good compliance were found in group B. Compared with group A, the D/W ratio of lung tissues in group B was higher (P < 0.05). In both groups, the pulmonary vein partial pressure of oxygen reached the peak at 2 h after perfusion, which did not significantly differ between two groups (P > 0.05). In group B, the pulmonary artery pressure was increased at a lower speed and significantly lower after perfusion, and the lactic acid level in the perfusate was significantly lower than those in group A (all P < 0.05). In group A, the alveolar structure was largely destroyed and the cells was rare. In group B, the alveolar structure was relatively normal without evident cell edema. The incidence of cell apoptosis of donor lung was high in group A, whereas no obvious cell apoptosis of donor lung was noted in group B. After perfusion for 4 h, the levels of monocyte chemoattractant protein (MCP)-1 and IL-6 were significantly increased, the IL-4 levels were remarkably decreased (all P < 0.05), but the levels of tumor necrosis factor (TNF)-α, IL-1α and inducible nitric oxide synthase (iNOS) did not significantly change in both groups (all P > 0.05). Conclusions IL-10 may improve the function of donor lung after EVLP in rat of cardiac death by reducing cell apoptosis.

Interpretation of Guide to the Quality and Safety of Organs for Transplantation(6th edition): identification and referral of potential donors / 器官移植

Organ shortage is one of the important factors restricting the development of human organ transplantation. The identification and referral of potential donors determine the total scale of organ donation. Whether potential donors can be identified and referred is the most important reason for the difference of organ donation rates in different regions. This paper interprets the chapter of the identification and referral of potential donors in the Guide to the Quality and Safety of Organs for Transplantation (6th edition) issued by European Union in order to provide reference for the staff of organ procurement organization and related medical personnel in China and improve the organ donation rate in China.

Progress on application of extracorporeal membrane oxygenation in donor maintenance / 器官移植

Organ transplantation is one of the effective methods for the treatment of end-stage diseases, but the lack of donors has hindered the development of organ transplantation. Extracorporeal membrane oxygenation (ECMO) can improve the hypoxia and hypoperfusion of organs, shorten the warm ischemia time, and maintain the function of donor organs effectively, in case of emergency or donor hemodynamic instability. It helps to make effective use of donor organs and benefit patients who are in urgent need of organ transplants. This article summarized the progress on application of ECMO in donor maintenance and provided suggestions for its application in organ transplantation.

Single-center data analysis of organ donation and utilization after citizen's death / 器官移植

Objective To get a knowledge of the current status of organ donation and utilization after citizen's death in Wuxi District, and thereby provide ideas and basis for further development of organ donation work in local areas. Methods Clinical data from 151 organ donors, included 37 successful donors and 114 potential donors, were retrospectively analyzed. The reasons for donation failure of potential donors were analyzed. The general information for successful donors was collected. And the information on organ donation and organ utilization in successful donors were analyzed. Results Among the 151 organ donors, 37 were successful donors, with the conversion rate reaching 24.5%. For the 114 donors with failed organ donation, the reasons for failure included family disagreement, failure to meet donation status criteria, insufficient evaluation time, and unresolved work injury disputes. The categories for organ donation included 34 cases of donation after brain death followed by cardiac death (DBCD), 3 cases of donation after brain death (DBD), and no case of donation after cardiac death (DCD). The reasons for death of donors includes 19 cases of craniocerebral trauma, 14 cases of stroke and 4 cases of others. Among the 37 cases of successful donors, the majority were floating population. A total of 154 major organs and tissues were donated, of which 124 were major organs. The number of major organs and tissues donated per citizen was (4.2± 1.6) and the number of major organs donated per citizen was (3.4± 1.1). The utilization rate of the 154 donated organs reached 96.7% (149/154), with Nanjing, Wuxi, Suzhou and Changzhou ranking the top 4 of organ distribution. Conclusions The rate for successful organ donation and conversion after citizen's death is low in Wuxi District. The organ donation work networks in local areas should be established. And organ donation promotion efforts and skills training for coordinators should be developed.

Analysis of early clinical efficacy of renal transplantation from extended criteria donor of the donation after cardiac death / 器官移植

Objective To compare the early clinical efficacy of renal transplantation between extended criteria donor (ECD) and standard criteria donor (SCD). Methods Clinical data of 85 recipients undergoing renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the types of donors, all recipients were divided into the ECD group (n=31) and SCD group (n=54). The level of serum creatinine (Scr), incidence of early complications and clinical prognosis within 3 months after renal transplantation were compared between 2 groups. Results No statistical significance was observed in the levels of Scr within 1 month after renal transplantation between the ECD group and SCD group (all P>0.05). At postoperative 60 and 90 d, the level of Scr in the ECD group was (189±97) and (175± 69) μmol/L respectively, significantly higher than (142±49) and (135±41) μmol/L in the SCD group (P=0.005 and 0.002). In the ECD group and SCD group, the incidence of acute rejection (AR) was 6% and 15%, the incidence of delayed graft function (DGF) was 23% and 19%, the incidence of pulmonary infection was 10% and 6%, the incidence of other early complications was 32% and 15%, respectively, no statistical significance was identified (all P>0.05). In the ECD group and SCD group, the survival rate of the recipient was 97% and 94%, the survival rate of the renal was 84% and 91%, no statistical significance was identified (all P>0.05). Conclusions Compared with the SCD, renal transplantation from ECD can achieve equivalent early clinical efficacy. In the present condition of serious deficiency of donor kidney, the application of ECD can enlarge the supply of the donor kidney.

Analysis of risk factors of early acute kidney injury after liver transplantation from DCD donor liver / 器官移植

Objective To analyze the risk factors of early acute kidney injury (AKI) after liver transplantation from donation after cardiac death(DCD) donor liver. Methods Clinical data of 184 donors and recipients undergoing liver transplantation from DCD donor liver were retrospectively analyzed. According to the incidence of early AKI, all participants were divided into the AKI and non-AKI groups. The patients in the AKI group were subject to AKI staging. Baseline data, preoperative, intraoperative and postoperative related parameters were statistically compared between two groups. The cumulative survival rate and clinical prognosis of patients in non-AKI group and AKI group with different staging were statistically analyzed by Kaplan-Meier curve analysis. Results Among 184 patients, 68 cases (37.0%) presented with early AKI after liver transplantation including 31 stage 1 AKI, 26 stage 2 AKI and 11 stage 3 AKI, mainly occurring within postoperative 3 d. Univariate analysis revealed that preoperative levels of albumin <35 g/L, preoperative levels of serum sodium ≤137 mmol/L, operation time>7.5 h, intraoperative hemorrhage volume>3 000 mL, intraoperative red cell infusion volume>15 U and intraoperative urine amount ≤100 mL/h were the risk factors of early AKI after liver transplantation (all P<0.05). Multi-variate Logistic regression analysis demonstrated that intraoperative red cell infusion >15 U was an independent risk factor of early AKI after liver transplantation [odds ratio(OR) 1.061, 95% confidence interval(CI)1.008-1.118,P=0.024].Result of Kaplan-Meier survival curve suggested that the cumulative survival rate was gradually reduced along with the aggravation of AKI with statistical significance (all P<0.05). Conclusions The incidence of early AKI following liver transplantation is relatively high. The severity of early AKI is intimately correlated with the short- and long-term prognosis of the recipients. A large quantity of intraoperative red blood cell infusion is an independent risk factor of AKI.

Protective effect of extracorporeal membrane oxygenation on donor kidneys from non-controllable donation after cardiac death / 器官移植

Objective To explore the protective effect of extracorporeal membrane oxygenation (ECMO) on donor kidneys from non-controllable donation after cardiac death (DCD). Methods A total of 60 non-controllable DCD donors were selected and divided into 3 groups randomly based on the in vivo perfusion time of ECMO: test group 1 received EMCO perfusion for 2 h, test group 2 for 4 h and test group 3 for 6 h, with 20 cases in each group. Corresponding recipients were also divided into 3 groups, with 20 cases in each group. Meanwhile, 20 recipients from donation after brain death (DBD) with stable circulatory function were randomly selected as control group. Incidence of delayed graft function (DGF), primary graft nonfunction (PNF) and acute rejection of the recipients in different groups was compared. The indexes including graft function recovery time, urine volume on day 1 and graft function within 1 year after renal transplantation were compared for the recipients in different groups. And 1-year survival rate of the recipients and grafts after renal transplantation was compared. Results Compared with the control group, various test groups presented no significant differences in the incidence of PNF, DGF and acute rejection (all P>0.05). Compared with the control group, graft function recovery time prolonged significantly in each test group, which presented statistically significant differences (all P<0.05), while the urine volume on day 1 and graft function within 1 year after renal transplantation presented no statistically significant difference in each test group (all P>0.05). The 1-year survival rate of the recipients and grafts after renal transplantation was 100％ in various test groups and control group, which presented no statistically significant difference (all P>0.05). Conclusions ECMO can protect donor kidneys effectively through assisting the circulatory or respiratory function of non-controllable DCD, and improve their utilization rate.