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World Journal of Transplantation Nov 2021Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate... (Review)
Review
Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering "transplantation" and "glucocorticoids". GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.
PubMed: 34868896
DOI: 10.5500/wjt.v11.i11.443 -
Transfusion and Apheresis Science :... Aug 2017Organ transplantation represents the preferred treatment option for many patients in terminal organ failure. The half-life of transplanted organs, however, is still far... (Review)
Review
Organ transplantation represents the preferred treatment option for many patients in terminal organ failure. The half-life of transplanted organs, however, is still far from being satisfactory with the vast majority of the organs failing within the first two decades following transplantation. At this stage, it has become apparent that rejection (prevalently mediated by humoral events) remains the primary cause of graft loss after the first year. In this light, studies are underway to better comprehend the immune events underlying graft rejection and novel immunosuppressive strategies are being explored. In this context, therapeutic apheresis techniques, that include therapeutic plasma exchange (TPE), immunoadsorption (IA) and extracorporeal photochemotherapy (ECP), represent an important adjunct in the current immunosuppressive armamentarium. This article briefly reviews our current understanding of the immune process underlying rejection of a solid organ transplant and describes the principal areas of application of therapeutic apheresis techniques in transplantation.
Topics: Graft Rejection; Hemofiltration; Humans; Organ Transplantation; Photopheresis; Plasma Exchange
PubMed: 28916402
DOI: 10.1016/j.transci.2017.07.005 -
International Journal of Molecular... Feb 2021Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during... (Review)
Review
Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.
Topics: Animals; Biomarkers; Graft Rejection; Graft Survival; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Organ Transplantation; Reperfusion Injury; Transplantation, Homologous; Tryptophan
PubMed: 33671985
DOI: 10.3390/ijms22041921 -
Transplantation Reviews (Orlando, Fla.) Oct 2016Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must... (Review)
Review
Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must take a lifelong cocktail of immunosuppressive medications that increase the risk for infections, malignancies and drug toxicities. Data from many animal studies have shown that recipients can be made tolerant of their transplanted organ by infusing stem cells, particularly hematopoietic stem cells, prior to the transplant. The animal data have been translated into humans and now several clinical trials have demonstrated that infusion of hematopoietic stem cells, along with specialized conditioning regimens, can permit solid organ allograft survival without immunosuppressive medications. This important therapeutic advance has been made possible by understanding the immunologic mechanisms by which stem cells modify the host immune system, although it must be cautioned that the conditioning regimens are often severe and associated with significant morbidity. This review discusses the role of hematopoietic stem cells in solid organ transplantation, provides an understanding of how these stem cells modify the host immune system and describes how newer information about adaptive and innate immunity might lead to improvements in the use of hematopoietic stem cells to induce tolerance to transplanted organs.
Topics: Animals; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immune Tolerance; Immunity, Innate; Organ Transplantation; Transplantation, Homologous
PubMed: 27553809
DOI: 10.1016/j.trre.2016.07.005 -
World Journal of Transplantation Sep 2016Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria,... (Review)
Review
Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.
PubMed: 27683627
DOI: 10.5500/wjt.v6.i3.460 -
Solid organ procurement from donors with carbon monoxide poisoning and/or burn--a systematic review.Burns : Journal of the International... Aug 2011Traditionally, carbon monoxide poisoning and/or burn are considered contraindications to organ procurement. Previously reported cases have shown mixed results and many... (Review)
Review
INTRODUCTION
Traditionally, carbon monoxide poisoning and/or burn are considered contraindications to organ procurement. Previously reported cases have shown mixed results and many have been redundantly reported in the literature.
METHODS
We performed a systematic review of all reported cases of organ transplantation procured from donors with carbon monoxide poisoning and/or burn to investigate whether these patients are suitable donors for solid organ transplantations.
RESULTS
Organ survival rates of reported organs were high (86%). All organs procured from donors with carbon monoxide poisoning and burn survived during follow-up. Mean donors' peak carbon monoxide levels were comparable for organs surviving or failing during follow-up (31 ± 2.7 vs. 29 ± 26.8; p=0.95). Eighty-seven per cent of organs procured from donors supported with inotropes or vasopressors prior to organ procurement and 91% of organs procured from donors who were cardiopulmonary resuscitated prior to organ procurement survived during follow-up.
CONCLUSIONS
Burn, carbon monoxide poisoning, high peak carbon monoxide-levels, use of inotropes or vasopressors or cardiopulmonary resuscitation prior to procurement are not contraindications for organ procurement and transplantation. New guidelines for burn units defining the special requirements for organ procurement from donors with carbon monoxide poisoning and/or burn are needed to raise the awareness for potential organ donors and to ultimately increase the donor pool and save patients' lives.
Topics: Burns; Carbon Monoxide Poisoning; Female; Graft Survival; Humans; Male; Tissue Donors; Tissue and Organ Procurement
PubMed: 21382666
DOI: 10.1016/j.burns.2011.02.002 -
Annals of Transplantation 2012Anemia is not only a feature of chronic kidney disease of native or grafted kidneys, but also is frequently found in liver and heart transplant recipients. End-stage... (Review)
Review
Anemia is not only a feature of chronic kidney disease of native or grafted kidneys, but also is frequently found in liver and heart transplant recipients. End-stage organ failure requiring transplantation is usually associated with failure or impaired function of other organs. Chronic kidney disease developing after non-renal solid organ transplantation is a significant issue, as reviewed previously. The degree of functional impairment in kidney function after non-solid organ transplantation and the rate of progression of CKD post-transplant depend to a large extent on pretransplant kidney function (ie, stage of preexisting CKD), the type of the transplanted organ, and the immunosuppressive protocol (use of calcineurin inhibitors), presence of comorbid conditions such as diabetes, hypertension, HCV infection, older age, surgical issues, and individual clinical features determining susceptibility to renal injury, even nephropathy resulting from BK virus infection, is presented.
Topics: Anemia; Humans; Organ Transplantation; Prevalence; Risk Factors
PubMed: 22743727
DOI: 10.12659/aot.883227 -
AACN Advanced Critical Care Jul 2016Within a little more than a decade, the transplant of human organs for end-stage organ disease became a reality. The early barriers to successful long-term graft and... (Review)
Review
Within a little more than a decade, the transplant of human organs for end-stage organ disease became a reality. The early barriers to successful long-term graft and patient survival were related to the inability to effectively control the immune system such that it would not attack the donor tissue but would still recognize and destroy invading organisms and cells. As immunosuppressive therapy has been refined and proper matching of donors and recipients has been improved, hyperacute rejection has become a rare occurrence and acute rejection has been markedly controlled. However, antibody-mediated rejection remains an important impediment to increased survival of transplanted organs. This article provides readers with a broad overview of the immune system, discusses mechanisms of transplant rejection, and details prevention, detection, and treatment of antibody-mediated rejection in solid organ transplant.
Topics: Adult; Aged; Aged, 80 and over; Antibodies; Female; Graft Rejection; Humans; Immunosuppression Therapy; Male; Middle Aged
PubMed: 27959315
DOI: 10.4037/aacnacc2016366 -
Infectious Disease Clinics of North... Sep 2018Complications of antimicrobial therapy, such as multidrug-resistant organisms and Clostridium difficile, commonly affect solid-organ transplant recipients and have been... (Review)
Review
Complications of antimicrobial therapy, such as multidrug-resistant organisms and Clostridium difficile, commonly affect solid-organ transplant recipients and have been associated with graft loss and mortality. Although opportunities are abundant, antimicrobial stewardship practices guiding appropriate therapy have been infrequently reported in transplant patients. A patient-centered, multidisciplinary structure, using established antimicrobial optimization principles, is needed to create nuanced approaches to protect patients and antimicrobials and improve outcomes.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Humans; Organ Transplantation; Postoperative Complications
PubMed: 30146022
DOI: 10.1016/j.idc.2018.04.003 -
Frontiers in Pharmacology 2021Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the... (Review)
Review
Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the transplant community. The preservation of organs during this process from donor to recipient is critical to the prognosis of both the graft and the recipient. At present, static cold storage, which is most widely used in clinical practice, not only reduces cell metabolism and oxygen demand through low temperature but also prevents cell edema and resists apoptosis through the application of traditional preservation solutions, but these do not improve hypoxia and increase oxygenation of the donor organ. In recent years, improving the ischemia and hypoxia of grafts during preservation and repairing the quality of marginal donor organs have been of great concern. Hemoglobin-based oxygen carriers (HBOCs) are "made of" natural hemoglobins that were originally developed as blood substitutes but have been extended to a variety of hypoxic clinical situations due to their ability to release oxygen. Compared with traditional preservation protocols, the addition of HBOCs to traditional preservation protocols provides more oxygen to organs to meet their energy metabolic needs, prolong preservation time, reduce ischemia-reperfusion injury to grafts, improve graft quality, and even increase the number of transplantable donors. The focus of the present study was to review the potential applications of HBOCs in solid organ preservation and provide new approaches to understanding the mechanism of the promising strategies for organ preservation.
PubMed: 34916938
DOI: 10.3389/fphar.2021.760215