Transplantation Reviews最新文献

Delayed graft function (DGF) is a common post-operative complication with potential long-term sequelae for many kidney transplant recipients, and hemodynamic factors and fluid status play a role. Fixed perioperative fluid infusions are the standard of care, but more recent evidence in the non-transplant population has suggested benefit with goal-directed fluid strategies based on hemodynamic targets. We searched MEDLINE, EMBASE, Cochrane Controlled Trials Registry and Google Scholar through December 2022 for randomized controlled trials comparing risk of DGF between goal-directed and conventional fluid therapy in adults receiving a living or deceased donor kidney transplant. Effect estimates were reported with odds ratios (OR) and pooled using random effects meta-analysis. We identified 4 studies (205 participants) that met the inclusion criteria. The use of goal-directed fluid therapy had no significant effect on DGF (OR 1.37 95% CI, 0.34–5.6; p = 0.52; I² = 0.11). Subgroup analysis examining effects among deceased and living kidney donation did not reveal significant differences in the effects of fluid strategy on DGF between subgroups. Overall, the strength of the evidence for goal-directed versus conventional fluid therapy to reduce DGF was of low certainty. Our findings highlight the need for larger trials to determine the effect of goal-directed fluid therapy on this patient-centered outcome.

Frailty is a clinical syndrome that is characterised by decline in multiple systems with associated decreased physiological reserve and ability to respond to stressor events. It is associated with greater healthcare burden. It is common in patients with end-stage renal disease (ESRD). Kidney transplantation is considered the optimal form of renal replacement therapy for suitable patients with ESRD. However, surgery and immunosuppression are physiological stresses that can disproportionately affect frail individuals. Frailty is emerging as a potentially important risk factor in patients waitlisted for kidney transplantation. Most of the published research to date in this area comes from a single transplant centre in the USA. Frailty, as measured using the Physical Frailty Phenotype (FP), is prevalent in waitlisted patients and has been associated with early hospital re-admission, prolonged length of stay, delayed graft function and increased mortality after kidney transplantation. However, although kidney transplantation is a substantial physiological stress to a patient's reserve, by restoring kidney function, kidney transplantation has also been shown to improve a patient's frailty status. The FP is the most studied tool in patients waitlisted for transplantation, but it has not been able to distinguish those whose frailty is improved by kidney transplantation.

In summary, there remain significant gaps in knowledge and uncertainties as to how to effectively use existing frailty measures to inform decision-making around kidney transplantation. Further research is needed to address these important gaps in the literature.

Any individual who has not attained the chronological age of legal majority as per national law is termed a minor. The concept of living donation (LD) has always been a subject of ethical debate and further compounding the controversy is the question of LD by minors. The decision for a minor to donate poses a special challenge as it involves a close family unit of parent-child relationship. Such an emotionally loaded situation wherein questions of attachment, perceived duties, moral obligation are likely to cloud a truly informed consent on the part of the minor to donation, who may find themselves in a vulnerable position. Furthermore, a minor's cognitive ability to comprehend the gravity of LD and when required defy parental coercion need to be elucidates before a minor is accepted for LD. Experts have set out stringent conditions which need to be met prior to the exceptional circumstance that a minor is considered for organ donation. Such donations should require parental permission, child's assent and the involvement of a paediatric-trained donor advocacy team. This article debates the question of minors acting as live donors from ethical, medical, psychosocial and legal viewpoints with an aim to present internationally defined circumstances when a minor may morally participate as a LD, thereby laying the foundation for future deliberations in this regard using traditional metrics to juxtapose divergent courses of action.

Background

Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early and accurate diagnosis is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest.

Methods

This systematic review of PubMed, Web of Science, and the ClinicalTrials.gov registry analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers.

Results

Thirteen studies were included in this systematic review. Various investigated miRNAs were upregulated in association with acute cellular rejection, like miR-122, miR-155, miR-181, miR-483-3p, and miR-885-5p, demonstrating great biomarker potential. Additionally, several studies conducted target gene analysis, revealing insights into cellular mechanisms linked to ACR. Moreover, various miRNA were also capable of predicting different organ complications following transplantation, expanding their versatility. Remaining challenges include the standardization of miRNA profiling, the need for functional validation, and the necessity for long-term studies.

Conclusion

The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.

Introduction

Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.

Methods

PubMed, EMBASE, Cochrane and MEDES were searched systematically for relevant articles. We included randomized controlled trials and observational studies published during the period from January 1990 to June 2021.

Results

From 212 screened records, we selected 19 papers including 1973 transplant recipients. Refractory infection ranged from 3 to 10% in studies with SOT recipients. The incidence of CMV resistance ranged from 1% to 36% in these patients. The incidence of CMV refractory infection in HSCT recipients ranged from 11 to 50%, while values for resistant infection ranged from 0% to 21%.

Conclusion

The wide range of definitions and values observed does not allow us to establish the true incidence of refractory CMV infection with or without resistances in SOT and HSCT patients in Spain. This review highlights the gap between clinical practice and clinical trials' definitions which needed to be updated to be easier followed in current clinical practice.

The British Transplantation Society (BTS) ‘Guideline on transplantation from deceased donors after circulatory death’ has recently been updated and this manuscript summarises the relevant recommendations in abdominal organ transplantation from Donation after Circulatory Death (DCD) donors, encompassing the chapters on liver, kidney, pancreas and islet cell transplantation.

The British Transplantation Society (BTS) ‘Guideline on transplantation from deceased donors after circulatory death’ has recently been updated and this manuscript summarises the relevant recommendations from chapters specifically related to law, ethics, donor consent and informing the recipient.

The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population.

Intestine transplantation (IT) is a critical treatment strategy for irreversible intestinal failure. Among all abdominal solid organ transplants, the intestine was the most vulnerable to ischemia and reperfusion injury (IRI). The static cold storage (SCS) technique is currently the most commonly used graft preservation method, but its hypoxia condition causes metabolic disorders, resulting in the occurrence of IRI, limiting its application in marginal organs. It is especially important to improve preservation techniques in order to minimize damage to marginal donor organs, which draws more attention to machine perfusion (MP). There has been much debate about whether it is necessary to increase oxygen in these conditions to support low levels of metabolism since the use of machine perfusion to preserve organs. There is evidence that oxygenation helps to restore intracellular ATP levels in the intestine after thermal or cold ischemia damage. The goal of this review is to provide an overview of the role of oxygen in maintaining environmental stability in the gut under hypoxic conditions, as well as to investigate the possibilities and mechanisms of oxygen delivery during preservation in intestine transplantation studies and clinical models.

Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged ≥65 years versus 23% for those aged 18–34 years) and are more vulnerable to immunosuppression-related complications. The number of liver transplant recipients ≥65 years has risen to 22% in Europe and the US, but limited information is available on the optimal immunosuppressive regimen for these patients. In this review, we discuss the appropriate management of immunosuppressive agents in older adults to minimize adverse events while avoiding acute rejection. The way the body processes drugs greatly depends on age. In the case of calcineurin inhibitor drugs, aging reduces hepatic metabolism, leading to changes in their pharmacokinetics. Corticosteroids also show decreased clearance as the patient ages. In severe cases of hypoalbuminemia, dose adjustment of mycophenolate acid derivatives may be necessary. However, the pharmacokinetic profiles of the mammalian target of rapamycin inhibitors, basiliximab, and rabbit anti-thymocyte globulin remain unaffected by age. Furthermore, age-related frailty may impact drug metabolism and require tailored interventions and closer follow-up. Although there is limited research, elderly liver transplant recipients require less immunosuppression with double or triple-agent regimens, lower exposure to calcineurin inhibitors, and a shorter course of corticosteroids. The usage of mammalian target of rapamycin inhibitors in older transplant populations has not been specifically investigated, and thus their usage should align with indications for younger patient groups.