Transplantation Reports最新文献

Background

Long term outcomes in transplant recipients experiencing recurrent focal segmental glomerulosclerosis (FSGS) remains poor. Despite early treatment, more than half lose their graft. The aims of this study were to evaluate treatment patterns, outcomes and to evaluate for predictors of treatment failure in recurrent FSGS.

Methods

This was a single center retrospective observational study. Between 1/2014 and 8/2019, 1860 kidney transplantations were performed at UCLA, 100 of which had end stage renal disease due to biopsy-proven FSGS. Comparative statistics were obtained and a multivariate analysis for graft outcomes in patients with recurrence was constructed. The primary outcomes were recurrent FSGS, allograft failure and pheresis dependence.

Results

Twenty-six of the 100recipients experienced FSGS recurrence. Patients with recurrence were younger (34.3 vs. 44.9, p = 0.001) and more likely to have had native nephrectomy (27% vs. 3%, p = 0.001). Gender, race, comorbidities, donor type, previous transplants and rates of rejection were similar between the recurrence and non-recurrence groups. Most patients received plasmapheresis (n = 24) with or without rituximab (11 vs. 13) which allowed for recovery of graft function in 18 patients (75%). Those experiencing a complete recovery required a median of 9 pheresis sessions, while those with graft failure (n = 3) or who became plasmapheresis-dependent (n = 5) required a median of 59 and 158 sessions, respectively. A multivariate analysis was constructed and no additional predictors of graft failure were encountered.

Conclusions

Patients with recurrent FSGS whoexperienced remissiondid so following a short course of plasmapheresis. The patients whose recurrence never resolved or who lost their graft underwent much longer courses of plasmapheresis. If this pattern of early durable response is validated in larger studies, there may be a future when transplant teams discuss the possibility of re-gifting based on treatment response to plasmapheresis following recurrence.

Background

Modern advancements have made organ transplantation an increasingly viable option for patients with organ failure. The resulting increases in patients awaiting transplant has resulted in significant morbidity and mortality due to increasing waiting time for transplant. The use of Donation after Circulatory Determination of Death (DCD) organ donors has been the most successful avenue to address the increased need for organ allografts. This review provides a brief history of DCD organ donation in the United States as represented by the experience of the Houston-based LifeGift Organ Procurement Organization (OPO).

Methods

Organ donation data from the Scientific Registry of Transplant Recipients (SRTR) and OPO specific data to include all available DCD donors for LifeGift were obtained for analysis. Trends in DCD donation were analyzed in the context of United Network for Organ Sharing policy.

Results

By the end of 2021 20% of organs donated in the United States were from DCD donors, in a steadily increasing trend since the mid-1990′s. Metrics utilized by UNOS to monitor organ donation rates and OPO performance do not clearly capture potential DCD donors. Individual OPOs have varying success in utilization of DCD donors, with OPOs like LifeGift focusing on increased DCD utilization.

Conclusion

DCD utilization remains the most successful avenue for increasing the deceased donor organ pool in the United States. Increased utilization of DCD organs by transplant centers and focused efforts by OPOs to promote DCD donation can improve the organ shortage nationally. Improved clarity in UNOS metrics can further facilitate OPO performance evaluation and promote further DCD donation in the United States.

How to translate basic research on surveillances for post organs transplantation facilitates the development of new laboratory tools for clinical application. Here, we provide the pertinent guide on how to analyze laboratory data in order to help clinicians to accurately determine the status of allograft in the recipient. We begin by discussing the molecular and cellular events that lead to allograft rejection across innate and adaptive immune responses. We focus on the allograft injury events that occur around the time of transplantation as well as molecular activities that ensue long before observable microscopic abnormalities are evident in biopsied samples. Then, we introduce and comment on new technologies involved in rejection detection from a practical point of view. This review outlines the current diagnostic development, describes unmet needs and challenges, and proposes new approaches for future directions.

After advancement of technical aspects, use of well-established and novel immunosuppressive therapies, and better pre and postoperative care, which resulted in high overall survival rates with liver transplantation, waiting list mortality has become the main issue for pediatric patients with end stage liver disease. Insufficient organ donors have become a challenging issue especially in the pediatric patient population, for whom size match of donor or graft is harder to achieve. In order to expand the donor pool and decrease the gap between the demand and supply of donor organs, use of donation after circulatory death (DCD) donors have been proportionally increased. In this chapter we aim to discuss current practices, issues and outcomes with DCD in pediatric liver transplantation, as well as future strategies for improvement of results.

The availability of thoracic organ transplantation as the treatment of choice for end-stage cardiac or pulmonary diseases is limited by the insufficient number of donor organs from brain dead donors, especially for organs where live-donation is not an option. Patients, who have not progressed to brain death, but have exhausted therapeutic options and life sustaining therapies are withdrawn can become donors with circulatory determination of death (DCD) when they meet criteria for the definition of this state. This approach can fulfill the wish of a patient to become an organ donor and also help to increase the number of donor organs. The DCD process exposes organs to prolonged warm ischemia that increases the possibility of primary graft dysfunction and failure. However, new technologies help in protecting the organs from cold preservation-related ischemia and facilitate resuscitation and monitoring of viability after the occurrence of the DCD-related ischemic insult. Herein, we review the opportunities and challenges in DCD thoracic organ transplantation, emerging techniques in preservation and monitoring of these organs and the potential effect of DCD thoracic organ transplantation on expanding the donor pool.

The sociocultural perception of Cardiopulmonary Death Donation by the population is an important issue, especially at this time when this type of donation is growing. However, the data that are currently available are insufficient to draw definitive conclusions on public reactions. Controlled organ donation after cardiocirculatory determination of death has generated an ethical and social debate since its implementation. The objective is to analyze the most relevant ethical-moral and social issues that involve this type of donation.

We were selected the 30 articles about this area with the PRISMA methodology. 72.2% of the articles that analyze the ethical conflicts on the withdrawal of life support treatment state that the staff that carries it out must be separate from the donation staff. 38.9% believe that it should be done in the ICM and 44.4% that it should be done by the ICM staff themselves. Regarding who should suggest controlled organ donation after cardiocirculatory determination of death, they all agree that it should be totally unrelated to ICM staff. 71.4% of the articles that analyze the use of premortem procedures justify their use based on scientific evidence and declare that they do not harm the potential donor. 42.1% accept the use of permanent circulatory cessation in determining death and 78.9% believe that a consensus should be reached on the waiting time in asystole. Despite some detractors, the use of ECMO is fully justified. Christian and Jewish culture are in favor of non-heart beating donation, but religious and economic objections continue to be raised in the Middle East. 80% of the articles that mention euthanasia classify it as a subject completely unrelated to controlled organ donation after cardiocirculatory determination of death

In conclusion, Organ donation after cardiocirculatory determination of death has experienced a boom in recent years and continues to lead to ethical-moral and social debate.

At the early days of organ transplantation before the diagnosis of brain death came in use only organs of non-heart-beating persons - who were the first donors after cardiac death (DCD) - could be taken for organ transplantation beside the living donors.

Organs from the first brain-dead donor were transplanted in 1963 in Belgium, five years later the famous Harvard Committee criteria were published. Following that in the Western world DCD was not used for organ transplantation, just in exceptional cases for several decades.

However, organ scarceness lead the way back to the idea of DCD. The original Maastricht classification discerns uncontrolled and controlled DCD in 4 categories from dead upon arrival through unsuccessful resuscitation attempt and awaiting cardiac death to cardiac arrest of a brain-dead person.

The time between the cessation of the of the circulation and the perfusion of the organ with the specific storage fluid is crucial for the possible use of the organs as transplants.

The recent studies explore the possibilities of the reconditioning of the organs to allow more and more of them to use for transplantation. The applicability is mostly needed in DCD cases. It is still open whether cold or warm perfusion, static or machine perfusion in continuous or pulsatile form would be the best for which organ.

Despite the evidence of the usefulness of this donor category, DCD is still not used universally. For example in Europe only one-third of the countries use DCD, the main reason is the underdevelopment of the infrastructural criteria in some of the countries, and the unsolved ethical and organizational challenges in others.

Background

Graft-versus-host disease (GVHD) continues to emerge as the topmost causative factor of the morbidity and mortality rate post hematopoietic stem cell transplantation. The graft cells attack the recipient host tissues resulting in acute or chronic GVHD that affect organs, including the lung, liver, skin, and gastrointestinal tract. Certain factors are considered to play a crucial role in the progression of the disease, such as antibodies produced by B cells, reduction in regulatory T cells, and immune tolerance disruption to self-antigen.

Main body

This review highlighted the pathophysiology of GVHD, clinical manifestation, stages of GVHD in different organs, and the significant role played by Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) in cytokine signalling, development, and function of several immune cells. Furthermore, we discussed the clinical efficacy of drugs, which comprises JAK inhibitors, monoclonal antibodies, and proteasome inhibitors that are widely used to treat GVHD.

Conclusion

Considering the progress recorded in identifying the therapeutic regimens for GVHD, novel and effective therapeutic approaches are much needed to alleviate the complication that arises post hematopoietic stem cell transplantation and reduce the morbidity and mortality rate of the disease.