Transplantation Reviews最新文献

Background

Treatment for de novo or recurrent tumors of liver transplantation (LT) recipients is challenging and immune checkpoint inhibitor (ICI) is recently well developed and could be a potentially effective option for this population. There remains limited evidence on the safety and efficacy of ICI therapy in LT recipients.

Methods

A systematic literature search was conducted on PubMed database through April 1, 2022, to identify publications reporting ICI treatment for malignant tumors in LT recipients. We summarized the allograft rejection, mortality, and tumor response of ICI treatment.

Results

24 articles with 41 LT recipients were identified. The age of LT recipients ranged from 14 to 78, 76.2% were male, 56.1% had recurrent HCC, and 87.8% received anti-PD-1 therapy. Allograft rejection occurred in 31.7% of patients, death was reported in 46.3% and 6 cases died secondary to allograft rejection. Progressive disease rate of this population was 48.8% and 10 patients responded to immunotherapy. Half of recipients with positive PD-L1 staining (4/8) experienced allograft rejection.

Conclusions

ICI therapy has potential therapeutic value on malignant tumors for LT recipients, accompanied by a high rate of allograft rejection and mortality. PD-L1 expression, type of ICI, and immunosuppression agent should be taken into consideration before initiation of immunotherapy. Further studies are needed to optimize this anticancer treatment approach in these patients.

Background

Kidney transplantation is the optimal treatment of end-stage renal disease. Extracellular vesicles (EVs) have tremendous therapeutic potential, but their role in modulating immune responses in kidney transplantation remains unclear.

Methods

We performed a systematic review and meta-analysis to investigate the therapeutic efficacy of EVs in preclinical kidney transplant models. Outcomes for meta-analysis were graft survival and renal function. Subgroup analysis was conducted between immune cell derived EVs (immune cell-EVs) and mesenchymal stromal cell derived EVs (MSC-EVs).

Results

Seven studies published from 2013 to 2021 were included. The overall effects showed that EVs had a positive role in prolonging allograft survival (standardized mean difference (SMD) = 2.00; 95% confidence interval (CI), 0.79 to 3.21; P < 0.01; I² = 94%), reducing serum creatinine (SCr) (SMD = -2.19; 95%CI, −3.35 to −1.04; P < 0.01; I² = 93%) and blood urea nitrogen (BUN) concentrations (SMD = -1.69; 95%CI, −2.98 to −0.40; P = 0.01; I² = 94%). Subgroup analyses indicated that only immune cell-EVs significantly prolonged graft survival and improve renal function but not MSC-EVs.

Conclusions

EVs are promising candidates to suppress allograft rejection and improve kidney transplant outcome. Immune cell-EVs showed their superiority over MSC-EVs in prolonging graft survival and improving renal function. For interpretation of the outcomes, additional studies are needed to validate these findings.

Introduction

The number of transplants in the world is growing, although there is a demand that exceeds supply. It is worth mentioning that the costs for obtaining organs are considered high. However, few studies have been developed on analyzing the costs of obtaining organs and tissues for transplants in order to support the decision-making of managers and health professionals.

Objective

To summarize the studies related to the cost of obtaining organs for transplants from a deceased donor.

Method

A systematic literature review was conducted in the following databases: PubMed, Cochrane Library CINAHAL, Virtual Health Library (BVS), SCOPUS, Web of Science and EMBASE, using the following descriptors: Costs and cost analysis; Donor Selection; Tissue and Organ Procurement; Tissue and Organ Harvesting; and Tissue Donors, in studies published until April 2021. The risk of bias assessment was performed using the Joanna Briggs Institute's Checklist for Economic Assessments. It was not possible to perform a meta-analysis due to the heterogeneity of the studies.

Results

A total of 1731 studies were identified, of which 11 were analyzed. The cost of kidneys in US dollars (USD) ranged between USD $1672 and USD $25,058. Obtaining a liver ranged from USD $586 to USD $44,478. Heart procurement ranged from USD $633 to USD $24,264. The combined heart-lung transplant ranged from USD $860 to USD $23,203. Obtaining the pancreas ranged from USD $413 to USD $29,708.

Conclusions

Cost of obtaining organs for transplants from a deceased donor is substantial and varies widely across different studies. The overall cost of failures to obtain organs is currently unknown. Understanding organ procurement expenses can help clarify areas in which organ and tissue procurement can improve in cost and efficiency.

Lung transplant (LTx) physicians are responsible for highly complex post-LTx care, including monitoring of kidney function and responding to kidney function loss. Better survival of the LTx population and changing patient characteristics, including older age and increased comorbidity, result in growing numbers of LTx patients with chronic kidney disease (CKD). CKD after LTx is correlated with worse survival, decreased quality of life and high costs. Challenges lie in different aspects of post-LTx renal care. First, serum creatinine form the basis for estimating renal function, under the assumption that patients have stable muscle mass. Low or changes in muscle mass is frequent in the LTx population and may lead to misclassification of CKD. Second, standardizing post-LTx monitoring of kidney function and renal care might contribute to slow down CKD progression. Third, new treatment options for CKD risk factors, such as diabetes mellitus, proteinuria and heart failure, have entered clinical practice. These new treatments have not been studied in LTx yet but are of interest for future use. In this review we will address the difficult aspects of post-LTx renal care and evaluate new and promising future approaches to slow down CKD progression.

Pigs, or Sus scrofa domestica, are commonly used animal models in translational transplantation research due to their anatomical, physiological, and immunological similarities to humans. In solid organ transplantation studies, immunosuppressive medications may be administered to pigs to prevent rejection. We provide an overview of the immunosuppressive regimens used in allogeneic solid organ transplantation in pigs, including heart, lung, kidney, bowel and cotransplanted organs and focus on the use of tacrolimus, mycophenolate mofetil, and corticosteroids.

Long-term immunosuppressant use in renal transplant recipients leads to dampened immune function and high susceptibility to opportunistic pathogens. Recently, the incidence of human parvovirus B19 (HPV-B19) infection after renal transplantation has increased, which may lead to pure red cell aplasia (PRCA), affect graft function, and lead to renal injury. After renal transplantation, the clinical manifestations of HPV-B19 infection are atypical, challenging the diagnosis and treatment. Therefore, we aimed to provide a comprehensive review of the existing literature to aid in the diagnosis and treatment of HPV-B19 infection after renal transplantation. To this end, we have described various aspects of HPV-B19 infection after renal transplantation ranging from the etiology, epidemiology, clinical manifestations, diagnosis, and treatment, to its prevention post renal transplant.

Biliary complications are one of the main concerns after liver transplantation, and to avoid these, the use of a T-tube has been advocated in biliary reconstruction. Most liver transplantation centres perform a biliary anastomosis without a T-tube to avoid the risk of complications and T-tube-related costs. Several meta-analyses have reached discordant conclusions regarding the benefits of using the T-tube. An umbrella review was performed to summarise quantitative measures about overall biliary complications, biliary leaks, biliary strictures and cholangitis associated with the T-tube use after liver transplantation. Published systematic reviews and meta-analyses related to the use of T-Tube in liver transplantation were searched and analysed. From the comprehensive literature search from PubMed, EMBASE and Cochrane Library databases on the 25th of October 2021, 104 records were retrieved. Seven meta-analyses and two systematic reviews were included in the final analysis. All the meta-analyses of RCT stated no differences in overall biliary complications and biliary leaks when using T-tube for a liver transplant (I² ≥ 90% and I² range 0–76%, respectively). The meta-analysis of the RCTs evaluating the risks of biliary strictures after liver transplantation showed that T-tube protects from the complication (I² range 0–80%). Biliary anastomosis without a T-tube has equivalent overall biliary complications and bile leaks compared to the T-tube reconstruction. The incidence of biliary strictures is attenuated in patients with T-tubes, and most meta-analyses of RCTs have very low heterogeneity. Therefore, the present umbrella review suggests a selective T-tube use, particularly in small biliary ducts or transplants with marginal grafts at high risk of post-LT strictures.

Due to the shortage of deceased and genetically- or emotionally-related living donors, living unrelated paid donor (LURpD) kidney transplantation has been considered; however, this practice may result in medical, ethical and social dilemmas, induce organ trading (commodification), and even criminal activities. Commodification also risks undermining public trust in the transplant system and impeding the development of proper altruistic or deceased donor programs by ignoring altruism, volunteerism, and dignity. However, despite many objections by authoritative organizations, black market practices are involved in up to 10% of all transplants worldwide.

The authors strongly discourage any payment or rewards for organ donation, and instead urge the governments of all countries to provide adequate and accessible kidney health care. However, it is an undeniable fact that paid-living donor transplantation is increasing despite all objections, disapprovals and regulations. We feel it as our responsibility not to ignore this uncertain and undesirable practice, but rather to underline the necessity for strict rules and prohibitions to minimize unacceptable medical, social and ethical risks as long as it exists. Furthermore, economic profit, be it direct or indirect, must not be the goal of those involved, and the employment of intermediaries must be avoided entirely. Additionally, the donor should be in a position where not donating has no detrimental effect on his/her future in any way (free agency).

In our view, every country has the obligation and responsibility to provide adequate kidney health care and to make kidney transplantation accessible to those in need. This provision is key to stop transplant tourism and commercialization of kidney transplantation. The nephrology community has a duty to establish structures that optimize organ availability within strict ethical limits. The legal position of LURpD varies considerably worldwide. Strictly respecting each country's legislation and local values is mandatory to minimize medical and ethical risks and controversies.

Among all the cells of innate immunity, natural killer (NK) cells are well-known for the fight against tumors and virally-infected cells. NK cells have been implicated in the pathogenesis of immune-mediated allograft damage, but mounting evidence suggests they can potentially promote allograft tolerance as well. In addition, NK cells express a wide variety of activating and inhibiting receptors, and the signals sent by these molecules, particularly killer cell immunoglobulin-like receptors (KIRs), determine their ultimate function. The role of KIRs and their human leukocyte antigen (HLA) class I ligands have been extensively investigated in hematopoietic stem cell transplantation (HSCT). Previous studies have suggested that, in the setting of solid organ transplantation, having certain KIR genes or KIR/HLA combinations probably affects allograft survival. Therefore, it may be helpful to analyze KIR/HLA combinations in donors and recipients to choose the optimal donor, anticipate harmful effects post-transplantation, and develop NK cell-based immunotherapies to enhance the success of solid organ transplantation. In this review, we will discuss the dual function of NK cells in solid organ transplantation, followed by a brief introduction to KIRs and the association of KIR and HLA genes with kidney, liver, and lung transplant outcomes.

The prevalence of coronary artery disease has increased in patients with end stage liver disease. In the near future, non-alcoholic steatohepatitis is expected to be the leading cause of end stage liver disease and shares common risk factors with coronary artery disease such as hypertension, hyperlipidemia, obesity and diabetes mellitus. At present, liver transplantation is the only definitive treatment for end stage liver disease, with post-operative mortality associated with the presence of coronary artery disease. Given the high prevalence of cardiovascular disease and the unique balance of pro-thrombotic and antithrombotic factors in patients with end stage liver disease, we sought to discuss the non-invasive and invasive diagnosis, medical and procedural management considerations and pre-transplant evaluation of coronary artery disease in patients with end stage liver disease.