Evolution and innovation of preservation fluid for donor liver / 器官移植

Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.

Ethical Thoughts on the Quality Evaluation of the Kidneys from Expanded Criteria Donors / 中国医学伦理学

In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.

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.

Ethical construction of recipients’ rights and interests protection in organ transplantation from expanded criteria donors / 器官移植

Under the background of severe shortage of donor organs and organ donation after citizen's death becoming the main source of donor organs in China, expanded criteria donor (ECD) has been widely applied in clinical practice. However, ECD has the disadvantages of basic diseases, old age, trauma, shock or infection, which will affect the quality of donor organs to varying degrees and become one of critical factors affecting clinical efficacy of organ transplantation. The recipients of ECD organ transplantation will also bear the additional risk and uncertainty of efficacy brought by ECD organs. Hence, it is necessary to pay attention to the protection of the recipients’ rights and interests. In this article, ethical issues faced by ECD organ transplantation in recipient protection and the shortcomings in the ethical review of organ ethics committee were reviewed, and suggestions on the ethical review institution and system construction of the rights and interests of organ transplantation recipients were elucidated, aiming to provide reference for promoting the advancement of ECD organ transplantation.

Chinese expert consensus on organ protection of transplantation (2022 edition) / 器官移植

Organ transplantation is the most effective treatment for end-stage organ failure, and voluntary donation after citizen's death is the only source of transplant organ in China. Clinically, transplant organ protection technique plays a critical role in improving the quality of transplant organs and the prognosis of recipients. On the basis of domestic and worldwide basic research and clinical practice of transplant organ protection and according to the Oxford evidence classification and GRADE system, the experts organized by Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Branch of Transplantation Group of Surgery of Chinese Medical Association and China Liver Transplant Registry Scientific Committee had compiled and published the Chinese Expert Consensus on Organ Protection of Transplantation (2016 edition) for liver, kidney, pancreas, small intestine, heart, lung transplant organs. With the support of China Liver Transplant Registry, National Trauma Medical Center, National Quality Control Center for Human Donated Organ Procurement, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation and National Center for Healthcare Quality Management in Liver Transplant combined with recent domeatic and worldwide clinical practice and research progress for organ transplantation and organ protection, the Chinese Expert Consensus on Organ Protection of Transplantation (2022 edition) has been published recently. This consensus focuses on updating the technical progress and evidence-based medicine of organ procurement, preservation, transport, and quality evaluation in clinical practice. Additionally, the content of composite tissue transplantation mainly including limb transplantation has also been covered. The aim is to promote the the scientific and standardized clinical organ transplantation.

Research progress on application of machine perfusion in quality maintenance of donor kidney from organ donation after citizen's death / 器官移植

Organ donation after citizen's death has become the main source of organ donation in China. However, the complexity of donor quality and the increasing proportion of expanded criteria donor (ECD) exert significant impact upon the availability of donor kidney and the long-term prognosis of recipients after kidney transplantation. Strengthening the quality maintenance and evaluation of donor kidney is of great significance for improving the quality of donor kidney, increasing the procurement and utilization of donor kidney and prolonging the long-term survival of recipients and kidney allografts. As one of the major approaches of organ preservation, machine perfusion preservation may not only prolong the preservation time and improve the quality of donor kidney, but also play a critical role in the repair and function evaluation of donor kidney. Based on literature review, several hot issues, corresponding treatment strategies and research progress on machine perfusion in the quality maintenance of donor kidney from organ donation after citizen's death were reviewed in this article, aiming to provide reference for selecting the optimal preservation method of donor kidney and enhancing the quality and utilization rate of ECD donor kidney.

Application of contrast-enhanced ultrasound in evaluation of donor kidney quality / 器官移植

In recent years, although the quantity of organ donation after citizen's death has been constantly increased, a large number of patients with end-stage renal diseases are waiting for kidney transplantation every year. The imbalance between donor and recipient is still one of the main problems affecting kidney transplantation in clinical practice. Therefore, it is of clinical significance to accurately evaluate the quality of donor kidney and fully utilize the expanded criteria donor kidney. Contrast-enhanced ultrasound has been gradually applied in the detection of multiple solid organs due to its safety, portability, real-time detection, quantification and other characteristics, and it also has promising application prospect in the evaluation of donor kidney quality. In this article, the advantages and limitations of current evaluation methods for donor kidney and current status and advantages of contrast-enhanced ultrasound in donor kidney evaluation were reviewed, and the application prospect of contrast-enhanced ultrasound in the evaluation of donor kidney quality was discussed, aiming to increase the methods and enhance the accuracy for donor kidney evaluation, and provide reference for rational use of expanded criteria donor kidney.

Ethical Thoughts on the Quality Evaluation of the Kidneys from Expanded Criteria Donors / 中国医学伦理学

In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.

Normothermic machine perfusion of kidney and ischemia-free kidney transplantation / 器官移植

To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.

Analysis of middle/long-term clinical efficacy of expanded criteria donor kidney transplantation / 中华器官移植杂志

Objective:To compare the medium/long-term prognosis of kidney transplant recipients with expanded criteria donor(ECD)versus standard criteria donor(SCD).Methods:From August 2011 to May 2017, a total of 506 cases underwent renal transplantation.Based upon baseline clinical data, they were divided into two groups of ECD(67 cases)and SCD(230 cases). And 1: 4 propensity score matching was employed for maximizing the elimination of selection bias influence on the results by rank-sum test.Results:There was no statistical difference existed between ECD and SCD donor kidney in acute rejection, delayed graft function and all-cause infection(all P>0.05). The value of eGFR of ECD donor kidney recipients was slightly lower than that of SCD group at Week 1 and Year 4 postoperatively( P<0.05). And there was no inter-group statistical significance in the fifth year( P=0.273). No significant inter-group difference existed in human/renal survival rate( P=0.143, P=0.076). Conclusions:Appropriate selection criteria and recipient selection criteria can make the application of ECD donor kidney safer and more scientific so as to benefit more patients.

Clinical application and progress on adult donor dual kidney transplantation / 器官移植

Full application of marginal donor organs is a critical method to expand donor pool and alleviate organ shortage. After accurate donor evaluation, allocation and recipient selection, adult donor dual kidney transplantation (DKT) can not only achieve equivalent clinical efficacy to single kidney transplantation (SKT), but also effectively reduce the discard rate of marginal donor kidney. In this article, the clinical application and progress on adult donor DKT were reviewed from the perspectives of the development situation, allocation standard, recipient selection, surgical methods and complications as well as clinical efficacy of DKT, aiming to provide reference and guidance for subsequent development of marginal donor DKT.

Application of dual hypothermic oxygenated machine perfusion in ex vivo split liver transplantation / 器官移植

The technology of split liver transplantation is becoming increasingly mature with rapid development. During ex vivo splitting, the depletion of intracellular energy sources [such as adenosine triphosphate (ATP)] and other metabolic disorders may lead to cell damage and dysfunction, which will be aggravated by reperfusion injury of liver transplantation, clinically manifested as postoperative complications and transplantation failure. To further improve the quality of donor liver in ex vivo split liver transplantation, research teams at home and abroad apply machine perfusion to enhance the quality of donor liver. In this article, the research progresses worldwide on machine perfusion of donor liver in ex vivo split liver transplantation were reviewed, and the application and prospect of dual hypothermic oxygenated machine perfusion (D-HOPE) in ex vivo split liver transplantation were elucidated, aiming to provide reference for increasing the source of donor liver for ex vivo split liver transplantation and further resolving the current status of donorliver shortage.

Research progress on risk factors of primary graft dysfunction after lung transplantation / 器官移植

Lung transplantation is the only effective approach to treat end-stage lung diseases. Nevertheless, early prognosis of lung transplant recipients is significantly worse than that of other solid organ transplant recipients. Primary graft dysfunction (PGD) is one of the main causes affecting clinical prognosis of the recipients. PGD is an early acute lung injury after lung transplantation, which is the main cause of early death of lung transplant recipients. Risk factors of PGD after lung transplantation consist of donor, recipient and operation, etc. In this article, the risk factors of PGD after lung transplantation were reviewed, aiming to provide reference for clinical practice.

Endovascular stenting with a drug-eluting stent of transplanted renal artery stenosis in a dual kidney transplanted patient / Tratamento endovascular com stent farmacológico em estenose de artéria renal transplantada de paciente com transplante renal duplo

Abstract Renal transplant remains the preferred therapy for end-stage renal disease (ESRD). Given the shortage of suitable donor kidneys, use of an expanded criteria donor (ECD) allows marginal kidneys to be transplanted; albeit at risk of increased graft failure due to lower nephron mass. To reduce the risk of graft failure, double kidney transplant (DKT) is advocated, with favorable outcomes. Transplant renal artery stenosis (TRAS) is one of the most common vascular complications following renal transplant. Unlike single kidney transplants, where TRAS usually presents with fluid overload, uncontrolled hypertension, and worsening kidney functions; it may be clinically silent in DKT patients since they have two functional transplanted kidneys. We hereby report a case of TRAS in a DKT patient who had 2 years of favorable clinical outcomes following successful endovascular stenting. He however recently died of COVID-19 associated pneumonitis.

Resumo O transplante renal continua sendo a terapia preferida para doenças renais em fase terminal. Dada a escassez de rins de doadores adequados, o doador com critérios expandidos permite que rins marginais sejam transplantados, embora haja um maior risco de falha do enxerto devido à diminuição da massa nefrótica. Para diminuir o risco de falha do enxerto, recomenda-se o transplante renal duplo (TRD), com resultados favoráveis. A estenose de artéria renal transplantada (EART) é uma das complicações vasculares mais comuns após o transplante renal. Ao contrário dos transplantes de rim simples, nos quais a EART geralmente se manifesta como sobrecarga de fluido, hipertensão descontrolada e piora das funções renais, ela pode ser clinicamente silenciosa em pacientes com TRD, pois eles têm dois rins funcionais transplantados. Relatamos aqui um caso de EART em um paciente com TRD que teve resultados clínicos favoráveis por dois anos após o sucesso do implante de stent endovascular. No entanto, ele morreu recentemente de pneumonite associada à covid-19.

Interpretation of Guide to the Quality and Safety of Organs for Transplantation (6th edition): organ procurement, preservation and transportation / 器官移植

The procurement, preservation and transportation of the donor organs directly affect the clinical prognosis of the recipients. The establishment of process optimization and quality control standards of organ procurement, preservation and transportation contributes to improving the quality and utilization rate of donor organs and reducing the medical risk. According to Guide to the Quality and Safety of Organs for Transplantation (6th edition) proposed by European Union, the 11th chapter of organ procurement, preservation and transportation was interpreted and summarized in this article.

Effect and research progress on continuous hypothermic machine perfusion in preservation of renal graft / 器官移植

Inevitable ischemia-reperfusion injury (IRI) occurred in organ donation after citizen's death often results in delayed graft function (DGF) after renal transplantation. Although the incidence of DGF had reduced to some extent due to continuous hypothermic machine perfusion (HMP) for renal graft using LifePort, DGF of renal graft remains a major clinical problem. In order to further reduce the incidence of DGF after renal transplantation, renal transplant surgeons should fully understand the role of continuous HMP in renal transplantation, continue to conduct more in-depth basic and applied research. This article mainly summarized the effect of continuous HMP on renal transplantation and its research progress.

Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death / 器官移植

Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.

Conversion therapy ofsirolimus in expanded standard renal transplant recipients / 中华器官移植杂志

Objective To evaluate the efficacy and safety of converting traditional triple immunosuppressive regimen into quadruple immunosuppressive regimen of low-dose tacrolimus plus sirolimus plus mycophenolic acid plus hormone in expanded criteria donor (ECD) renal transplant recipients .Methods A retrospective analysis was conducted for 39 patients undergoing extended standard kidney transplantation with conversion therapy from January 2015 to June 2018 .Renal function ,liver function ,blood lipid ,bone marrow suppression ,positive rate of urinary protein ,positive rate of urinary BK virus and other adverse reactions were analyzed .Results A total of 39 recipients fulfilled the inclusion criteria ,including 28 boys and 11 girls with an average age of (37 .69 ± 11 .07) years and a median postoperative conversion time of 6 months .As compared with pre-conversion therapy ,renal function and estimated glomerular filtration rate improved significantly at 1 month ,3 months ,6 months and 1 year (P<0 .05) .No significant difference existed in the level of blood lipid ,whole blood leukocyte or hemoglobin at pre and post-conversion ( P>0 .05) .No significant difference existed between AST and ALT at pre and post-conversion (P< 0 .05) . After conversion , the positive rates of urinary protein and BK virus urine declined . Subacute rejection occurred in 1 case after conversion .Addition of sirolimus was curative .No severe adverse reactions such as infection and diarrhea occurred in the remaining cases .Conclusions T he quadruple immunosuppressive regimen of low-dose tacrolimus plus sirolimus plus mycophenolic acid and hormone is both safe and effective for ECD recipients of renal transplantation .

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation / 中华医学杂志(英文版)

<p><b>Background</b>Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.</p><p><b>Methods</b>We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC) and Tac Cwere measured at the 1 week and the 1 month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.</p><p><b>Results</b>The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC at the 1 week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUClevel was <30 mg·h·L at the 1 week (15.0% vs. 44.4%) or the Tac Cwas <4 ng/ml at the 1 month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC at the 1 week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac Cat the 1 month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05).</p><p><b>Conclusions</b>Low-level exposure of MPA and Tac Cin the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC <30 mg·h·L and Tac C <4 ng/ml should be avoided in the first few weeks after transplantation.</p>

The Need for New Donor Stratification to Predict Graft Survival in Deceased Donor Kidney Transplantation

PURPOSE: The aim of this study was to determine whether stratification of deceased donors by the United Network for Organ Sharing (UNOS) criteria negatively impacts graft survival. MATERIALS AND METHODS: We retrospectively reviewed deceased donor and recipient pretransplant variables of kidney transplantations that occurred between February 1995 and December 2009. We compared clinical outcomes between standard criteria donors (SCDs) and expanded criteria donors (ECDs). RESULTS: The deceased donors consisted of 369 patients. A total of 494 transplant recipients were enrolled in this study. Mean age was 41.7±11.4 year (range 18–69) and 273 patients (55.4%) were male. Mean duration of follow-up was 8.8±4.9 years. The recipients from ECD kidneys were 63 patients (12.8%). The overall mean cold ischemia time was 5.7±3.2 hours. Estimated glomerular filtration rate at 1, 2, and 3 years after transplantation were significantly lower in ECD transplants (1 year, 62.2±17.6 vs. 51.0±16.4, p0.05), although patient survival was lower in ECDs than SCDs (Log rank test, p=0.011). CONCLUSION: Our data demonstrate that stratification by the UNOS criteria does not predict graft survival. In order to expand the donor pool, new criteria for standard/expanded donors need to be modified by regional differences.