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Arquivos Brasileiros de Cirurgia... 2024Lower urinary tract abnormalities are directly implicated in the etiology of renal dysfunction in 6 to 24% of dialytic patients. These patients require bladder capacity... (Review)
Review
Lower urinary tract abnormalities are directly implicated in the etiology of renal dysfunction in 6 to 24% of dialytic patients. These patients require bladder capacity and compliance readjustment before being considered viable candidates for renal transplantation. Vesical augmentation surgeries often involve the use of intestinal segments. Although these procedures can effectively restore bladder capacity and compliance, they present various issues related to maintaining mucous absorption and secretion capacity. Acidosis, recurrent urinary tract infections, and stone formation are extremely common, leading to frequent hospitalizations and graft function loss. Urinary tissue is certainly ideal for these reconstructions; however, bladder augmentation using ureter and renal pelvis are feasible only in a minority of cases. Experimental studies have been conducted to establish the groundwork for vascularized bladder transplantation. Last year, for the first time, this procedure was performed on a brain-dead patient. During this intervention, cystectomy was performed with preservation the vascular pedicle, followed by organ reimplantation. The graft remained viable for a period of 12 hours post-transplant. However, this intervention utilized a robotic platform, making it less reproducible in a multi-organ procurement setting as well as for most transplant centers. Moreover, it is debatable whether the benefits of exclusive bladder transplantation outweigh the risks associated with immunosuppression. For patients needing renal transplantation and requiring lower urinary tract reconstruction, however, utilizing the donor's bladder may offer an attractive alternative, avoiding the inherent complications of enterocystoplasty without increasing immunological risk. Combined kidney and bladder transplantation has the potential to emerge as the next frontier in abdominal organ transplants.
Topics: Humans; Urinary Bladder; Kidney Transplantation; Organ Transplantation
PubMed: 38896703
DOI: 10.1590/0102-6720202400015e1808 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
American Journal of Transplantation :... Jun 2017With 40 donors and more than 100 transplant procedures per million population in 2015, Spain holds a privileged position worldwide in providing transplant services to... (Review)
Review
With 40 donors and more than 100 transplant procedures per million population in 2015, Spain holds a privileged position worldwide in providing transplant services to its patient population. The Spanish success derives from a specific organizational approach to ensure the systematic identification of opportunities for organ donation and their transition to actual donation and to promote public support for the donation of organs after death. The Spanish results are to be highlighted in the context of the dramatic decline in the incidence of brain death and the changes in end-of-life care practices in the country since the beginning of the century. This prompted the system to conceive the 40 donors per million population plan, with three specific objectives: (i) promoting the identification and early referral of possible organ donors from outside of the intensive care unit to consider elective non-therapeutic intensive care and incorporate the option of organ donation into end-of-life care; (ii) facilitating the use of organs from expanded criteria and non-standard risk donors; and (iii) developing the framework for the practice of donation after circulatory death. This article describes the actions undertaken and their impact on donation and transplantation activities.
Topics: Brain Death; Humans; Organ Transplantation; Tissue Donors; Tissue and Organ Procurement
PubMed: 28066980
DOI: 10.1111/ajt.14104 -
Journal of the American College of... Jun 2020
Topics: Air Pollution; Heart Transplantation; Humans; Organ Transplantation; Tissue and Organ Procurement
PubMed: 32498819
DOI: 10.1016/j.jacc.2020.04.025 -
Transplant International : Official... Apr 2017Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient... (Review)
Review
Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n = 2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique. Nine (32%) reported patient involvement. The 336 research priorities addressed the following: organ donation [43 priorities (14 studies)]; waitlisting and allocation [43 (10 studies)]; histocompatibility and immunology [31 (8 studies)]; immunosuppression [21 (10 studies)]; graft-related complications [38 (13 studies)]; recipient (non-graft-related) complications [86 (14 studies)]; reproduction [14 (1 study)], psychosocial and lifestyle [49 (7 studies)]; and disparities in access and outcomes [10 (4 studies)]. The priorities identified were broad but only one-third of initiatives engaged patients/caregivers, and details of the process were lacking. Setting research priorities in an explicit manner with patient involvement can guide investment toward the shared priorities of patients and health professionals.
Topics: Biomedical Research; Caregivers; Delphi Technique; Focus Groups; Graft Rejection; Graft Survival; Health Services Accessibility; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Living Donors; Organ Transplantation
PubMed: 28120462
DOI: 10.1111/tri.12924 -
American Journal of Transplantation :... Mar 2020Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and... (Review)
Review
Allergy transfer upon solid organ transplantation has been reported in the literature, although only few data are available as to the frequency, significance, and management of these cases. Based on a review of 577 consecutive deceased donors from the Swisstransplant Donor-Registry, 3 cases (0.5%) of fatal anaphylaxis were identified, 2 because of peanut and 1 of wasp allergy. The sera of all 3 donors and their 10 paired recipients, prospectively collected before and after transplantation for the Swiss Transplant Cohort Study, were retrospectively processed using a commercial protein microarray fluorescent test. As early as 5 days posttransplantation, newly acquired peanut-specific IgE were transiently detected from 1 donor to 3 recipients, of whom 1 liver and lung recipients developed grade III anaphylaxis. Yet, to define how allergy testing should be performed in transplant recipients and to better understand the impact of immunosuppressive therapy on IgE sensitization, we prospectively studied 5 atopic living-donor kidney recipients. All pollen-specific IgE and >90% of skin prick tests remained positive 7 days and 3 months after transplantation, indicating that early diagnosis of donor-derived IgE sensitization is possible. Importantly, we propose recommendations with respect to safety for recipients undergoing solid-organ transplantation from donors with a history of fatal anaphylaxis.
Topics: Cohort Studies; Humans; Immunoglobulin E; Organ Transplantation; Peanut Hypersensitivity; Retrospective Studies
PubMed: 31535461
DOI: 10.1111/ajt.15601 -
Seminars in Immunopathology Jan 2023Solid organ transplantation (SOT) is the standard of care for end-stage organ disease. The most frequent complication of SOT involves allograft rejection, which may... (Review)
Review
Solid organ transplantation (SOT) is the standard of care for end-stage organ disease. The most frequent complication of SOT involves allograft rejection, which may occur via T cell- and/or antibody-mediated mechanisms. Diagnosis of rejection in the clinical setting requires an invasive biopsy as there are currently no reliable biomarkers to detect rejection episodes. Likewise, it is virtually impossible to identify patients who exhibit operational tolerance and may be candidates for reduced or complete withdrawal of immunosuppression. Emerging single-cell technologies, including cytometry by time-of-flight (CyTOF), imaging mass cytometry, and single-cell RNA sequencing, represent a new opportunity for deep characterization of pathogenic immune populations involved in both allograft rejection and tolerance in clinical samples. These techniques enable examination of both individual cellular phenotypes and cell-to-cell interactions, ultimately providing new insights into the complex pathophysiology of allograft rejection. However, working with these large, highly dimensional datasets requires expertise in advanced data processing and analysis using computational biology techniques. Machine learning algorithms represent an optimal strategy to analyze and create predictive models using these complex datasets and will likely be essential for future clinical application of patient level results based on single-cell data. Herein, we review the existing literature on single-cell techniques in the context of SOT.
Topics: Humans; Organ Transplantation; Immunosuppression Therapy; Immune Tolerance; T-Lymphocytes; Biomarkers; Graft Rejection
PubMed: 35980400
DOI: 10.1007/s00281-022-00958-0 -
American Journal of Transplantation :... Apr 2022Our understanding of the involvement of the gut microbiota (GM) in human health has expanded exponentially over the last few decades, particularly in the fields of... (Review)
Review
Our understanding of the involvement of the gut microbiota (GM) in human health has expanded exponentially over the last few decades, particularly in the fields of metabolism, inflammation, and immunology. Immunosuppressive treatment (IST) prescribed to solid organ transplant (SOT) recipients produces GM changes that affect these different processes. This review aims at describing the current knowledge of how IST changes the GM. Overall, SOT followed by IST results in persistent changes in the GM, with a consistent increase in proteobacteria including opportunistic pathobionts. In mice, Tacrolimus induces dysbiosis and metabolic disorders, and alters the intestinal barrier. The transfer of the GM from Tacrolimus-treated hosts confers immunosuppressive properties, suggesting a contributory role for the GM in this drug's efficacy. Steroids induce dysbiosis and intestinal barrier alterations, and also seem to depend partly on the GM for their immunosuppressive and metabolic effects. Mycophenolate Mofetil, frequently responsible for digestive side effects such as diarrhea and colitis, is associated with pro-inflammatory dysbiosis and increased endotoxemia. Alemtuzumab, m-TOR inhibitors, and belatacept have shown more marginal impact on the GM. Most of these observations are descriptive. Future studies should explore the underlying mechanism of IST-induced dysbiosis in order to better understand their efficacy and safety characteristics.
Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Immunosuppression Therapy; Mice; Organ Transplantation; Tacrolimus
PubMed: 34510717
DOI: 10.1111/ajt.16836 -
Transplantation Nov 2021Humoral allogeneic immunity driven by anti-HLA donor-specific antibodies and antibody-mediated rejection (AMR) significantly impede prolonged survival of organ... (Review)
Review
Humoral allogeneic immunity driven by anti-HLA donor-specific antibodies and antibody-mediated rejection (AMR) significantly impede prolonged survival of organ allografts after transplantation. Although the importance of T follicular helper (TFH) cells in controlling antibody responses has been long established, their role in directing donor-specific antibody generation leading to AMR was only recently appreciated in the clinical setting of organ transplantation. In this review, we provide a comprehensive summary of the current knowledge on the biology of human TFH cells as well as their circulating counterparts and describe their pivotal role in driving humoral alloimmunity. In addition, we discuss the intrinsic effects of current induction therapies and maintenance immunosuppressive drugs as well as of biotherapies on TFH cells and provide future directions and novel opportunities of biotherapeutic targeting of TFH cells that have the potential of bringing the prophylactic and curative treatments of AMR toward personalized and precision medicine.
Topics: Graft Rejection; Hematopoietic Stem Cell Transplantation; Humans; Immunity, Humoral; Organ Transplantation; T Follicular Helper Cells; T-Lymphocytes, Helper-Inducer
PubMed: 33909968
DOI: 10.1097/TP.0000000000003776 -
Annals of Transplantation Feb 2019Organ transplantation is one of the most critical ethical topics in law and medicine and a matter of debate in various countries. Lack of organs for engraftment to meet... (Review)
Review
Organ transplantation is one of the most critical ethical topics in law and medicine and a matter of debate in various countries. Lack of organs for engraftment to meet the existing demand has resulted in a substantial crisis due to organ shortage and a rise in the critical conditions of certain waitlisted patients, as well as increased mortality of patients while waiting. Organ shortages for transplantation raised the issue of procurement of organs not only from living donors and cadaveric donors after brain death, but also after circulatory death. Renewed interest in donation after circulatory death started in the 1990s, and has been on the rise in recent years, reaching up 40% of donation in some countries. Both legislation on and practice of donation after circulatory death differ significantly throughout the world. Lack of unified guidelines and regulations have challenged the medical, ethical, legal, and transplant communities. Moreover, studies on legal aspects of donation after circulatory death are still lacking. In this review, we present selected legal issues in regulation of donation after circulatory death, and we address the most important legal challenges in this regard with particular attention to category III of donors after circulatory death.
Topics: Brain Death; Humans; Organ Transplantation; Poland; Tissue Donors; Tissue and Organ Procurement
PubMed: 30773527
DOI: 10.12659/AOT.912567