Transplantation Reports最新文献

Introduction

Organ shortage represents one of the main issues associated with lung transplantation (LTx). Over the years, in an attempt to increase the donor pool, the use of donors after cardiac death (DCDs) has gradually increased, with good results that bode well for their wider use in the future.

Methods

In this work, our experience with DCDs is presented. In addition, a brief literature review on controlled (c) and uncontrolled (u) DCDs was performed on the studies published in the last four years.

Results

From 2018 to 2022 our center performed three LTx with DCDs. All the donors were uDCDs (Maastricht class II). The median warm ischemic time of the graft was 160 min. In all the three LTx, lungs were reconditioned using portable Ex-Vivo-Lung-Perfusion (EVLP) system (Organ Care System, OCS, TransMedics) for a median time of 535 min. All the three LTx were performed with an intraoperative veno-arterial extra-corporeal membrane oxygenation (V-A ECMO), which was prolonged postoperatively in one patient.

Grade 3 primary graft disfunction (PGD) at 72 h was observed in one patient. No signs of acute rejection were observed in any patient at the surveillance transbronchial biopsies. One patient died 317 after LTx for consequences of a lung adenocarcinoma diagnosed in the native lung, while the other two are still alive with a preserved graft function.

Summary

The most recent studies confirm similar results between DCDs and DBDs in terms of survival and graft function. Good results can also be achieved in uDCDs if standardized protocols are followed and graft function is monitored by EVLP.

Hence, the use of DCDs represents a valid solution to expand the donor pool.

Chronic immunosuppressive therapy is critical to all transplant patients to help prevent rejection, chronic injury and loss of allograft. Tacrolimus is used as immunosuppression in more than ninety percent of kidney transplant recipients, and requires drug level monitoring. It is known that many prescribed medications can alter tacrolimus metabolism and lead to unpredictable levels that may expose patients to the above-mentioned complications. However, the use of over-the-counter medications is often overlooked. Here, we present a case report in which over-the-counter calcium carbonate significantly affected the patient's tacrolimus metabolism leading to unpredictable levels.

Allogeneic blood and marrow transplant (BMT) is used to transplant a new immune system in patients with hematologic malignancies or immune-mediated disease. BMT patients require initial immune suppression to prevent graft rejection and graft versus host disease (GVHD). Tacrolimus and cyclosporine are calcineurin inhibitors (CNI) and methotrexate is an antimetabolite used to mitigate this immune response. Tacrolimus has data supporting oral dose variation based on pharmacogenomic (PGx) studies for Intermediate Metabolizers (IM) and Poor Metabolizers (PM) on studies done in kidney transplant patients. There are fewer studies on BMT patients in this field, and even less on the variability of IV to oral conversion dosing and first pass metabolism effect based on PGx profiles. Methotrexate has been shown to have PGx mutations affecting its metabolism at higher dosing used for chemotherapy, but its impact on BMT patient dosing is not well-defined. Based on our study, we found statistically significant variability in Tacrolimus concentration based on drug assay levels compared with dosing for Intravenous (IV) and oral formulation based on PGx predicted phenotypes. We further noted a profound effect on first pass metabolism when transitioning between IV and oral dosing of Tacrolimus based on PGx predicted phenotypes. The average oral dose in predicted IM phenotypes divided by the IV dose was 2.68. For the predicted PM phenotype, the average oral dose divided by the IV dose was 1.18. The p-value in a two-tailed nonparametric T-test with equal variance assessing the conversion factor from IV to oral dosing in predicted IM versus PM phenotypes was significant with a p-value of 0.002. Methotrexate metabolism did not seem to be affected by PGx mutations at the doses used for BMT GVHD prevention.

With the continued deficit of available organs for transplantation, optimal care of the brain-dead and cardiac death donor is essential to optimize quality and quantity of precious organs. Anesthesiologists are a critical part of the perioperative surgical retrieval process, although individually, may rarely care for a donor. Prospective data to inform specific clinical practices is sparse although educational resources exist to guide anesthesiologists with ethical or clinical questions and protocols from intensive care units and organ procurement organizations serve as useful templates for maintenance of organ function. Pre-surgical resuscitation, optimization and homeostatic strategies should be continued into the operating room. Cautious titration of low dose anesthetic and analgesic agents may be required to blunt sympathetic and spinal reflexes but should not aggravate hypotension and muscle relaxation is recommended to facilitate surgical exposure. Anesthesiologists should be aware of procedural and pharmaceutical aspects of the donation process, including re-intubation of a deceased donor after death is confirmed when lung retrieval is planned.

The disproportion between the number of patients on the kidney transplant waiting list and the actual donors pool represents a primary issue for the international Transplant community. The development of donation after circulatory death (DCD) programs has been associated with a remarkable increase in organs procurement and transplants activities across the globe. However, effective DCD donation and transplantation require the resolution of several legal, ethical, deontological, logistical, and technical issues. In Italy, the major obstacle to this very specific type of dation was represented by the 20-minute no-touch period for the declaration of death by cardio-circulatory criteria established by the Italian legislation. Following the encouraging results obtained with the use of in situ Normothermic Regional Perfusion in the setting of a single-center exploratory trial performed between 2008 and 2013 (Alba project), the Comitato Nazionale per la Bioetica and the Centro Nazionale Trapianti eventually managed to start a national-scale controlled and uncontrolled DCD program. We herein describe the Italian DCD KT program with a special focus on the most crucial and peculiar aspects of the national organ donation and allocation process.

Background

Lung transplantation (LT) demand outpaces supply. Consequently, extended criteria for donor selection are used, resulting in LT from donors with a history of substance use (SU). The aim of this study is to assess the association between donor SU and short-term LT outcomes.

Methods

We obtained recipient and donor data for LTs performed between January 2014 to January 2019 from electronic health records and the United Network for Organ Sharing (UNOS) database. We defined SU as cigarette/e-cigarette smoking, illicit SU (cannabis, cocaine, opioids, amphetamines), or heavy alcohol use (2+ alcoholic drinks per day). Our primary outcome was late high-grade primary graft dysfunction (PGD), which we defined as grade 2-3 PGD between 48-72 hours post-LT. Secondary outcomes included mechanical ventilation (MV) hours, intensive care unit (ICU) length of stay (LOS), hospital LOS, number of bronchoscopies, cumulative acute rejection (CAR) score in the first year after LT, and overall survival (OS).

Results

A total of 352 LTs were included in this study. On multivariable regression, we found that any donor cigarette smoking was associated with increased odds of late high grade PGD (p=0.021), while any donor cannabis use was associated with reduced odds of late high grade PGD (p=0.002). There was no association between any donor SU and secondary outcomes.

Conclusions

Donor cigarette use was associated with higher risk for PGD. Our findings may suggest a history of donor cannabis use and other illicit SU are not associated with PGD or worse OS.

In Japan, since the revision of the Organ Transplant Law in July 2010, donation after brain death (DBD) has increased, while donation after cardiac death (DCD), which has been mainly used by kidney transplantation, has decreased. The number of DCD donors decreased from 98 in 2009 to 28 in 2019. There is no clear reason for the decrease in DCD donors. Furthermore, since 2020, there has been a marked decrease in DCD due to the influence of the COVID-19 pandemic. On the other hand, the outcomes after kidney transplantation from DCD donors are improving year by year. The outcomes of kidney transplantation from DCD donors in Japan are comparable to those of kidney transplantation from DBD donors in Western countries. In order to further improve transplantation outcomes from DCD donors, the clinical introduction of continuous machine perfusion preservation technology, for the purpose of reducing ischemic reperfusion injury, is expected in Japan.

Kidney transplantation is the best treatment available for patients with end-stage renal disease. There are three categories of donors: living donors (LD), brain death (DBD) or cardiac death (DCD) kidney donors. In this review we analyze the current scenario of DCD renal transplantation in Europe and in Italy. In Italy DCD donation has not yet been significantly developed because of the obstacle of the 20 min no touch period after cardiac arrest, before cannulating and perfusing organs to be recovered. This procedure is requested by current Italian law and is not going to be changed in the near future.

We analyze problems rising from this law and suggest possible solutions.

Transplantation remains the optimum treatment for many patients. The availability of donor organs has failed to keep pace with demand, resulting in an ever-increasing waiting list of potential recipients. Using organs from donation after circulatory death (DCD) donors is one of the strategies available to increases the number of donor organs. On one hand in many countries DCD donation has gained popularity and the outcomes are comparable to organ transplantations following brain death donation, but on the other hand still a lot of problems exist for both controlled and uncontrolled DCD regarding ethical and legal issues of DCD program in several regions. There are guidelines though available for the whole process of DCD donation and transplantation from national transplant societies and anaesthesiology societies.

The aim of this paper was to review the DCD activity and the possibilities to improve the number of organ transplantation in the Asian region based on literature search.

A novel donation concept, namely organ donation after brain death followed by circulatory death (DBCD) has been initiated in many Asian countries to help increase the available organs for transplantation since around 2011. The reason why there are so many DBCD donors is because brain death law has not been approved on a national level in most of the Asian countries, and culturally many relatives of deceased donors can only accept donor death when heart beating is irreversibly arrested.

Based on this review there is a need to implement DCD transplant programs and to establish reliable protocols for this type of donation across all the Asian countries to increase the number of transplantations.