Progress and Recent Advances in Solid Organ Transplantation

There have been recent significant improvements in the short-term survival of solid organ transplantation patients due to advances in immunosuppression and transplant techniques. However, long-term graft survival has still lagged behind other outcomes and has now become one of the main problems in solid organ transplantation.For this Special Issue, we invited researchers and clinicians to submit studies on solid organ transplantation. These have provided us with additional knowledge and skills that will ultimately help us to improve outcomes after solid organ transplantation

FK506 in solid organ transplantation

FK506 (Prograf) is a new immunosuppressive agent, recently approved for use in solid organ transplants. The first use of FK506 was for the indication of refractory liver allograft rejection. This revealed a marked ability to reverse ongoing rejection, even in cases where chronic changes were observed. Between 50 and 70% of patients converted to FK506 had shown improvement. In long-term follow-up of patients with chronic rejection, 75% of patients were still alive at 3 years following FK506 conversion, and 65% of liver allografts were still functioning. FK506 has been compared to cyclosporine in primary liver transplantation. In the three randomized trials, freedom from rejection was statistically greater in the FK506-treated group, as compared to the cyclosporine-treated group. By intent-to-treat analysis, the patient and graft survival in the FK506 group was the same or better than the cyclosporine group. The good results in the cyclosporine limb was due, in part, to the ability of FK506 to treat rejection in the cyclosporine group. Freedom from steroid use, and the lower incidence of hypertension, were prominent features of FK506 patients. FK506 has been used for rescue of rejecting kidney allografts, with results similar to the liver transplant trials. When used as primary immunosuppression, FK506 was shown to be effective, as measured by graft survival. FK506-based immunosuppression has also been used in primary heart transplantation, as well as for primary adult pulmonary transplantation. Results from these small series of patients are equally encouraging. The results of these studies suggest that FK506 is effective for solid organ transplantation. Both FK506 and cyclosporine administration have been associated with side effects, many of which are similar, and some of which are peculiar to a given organ transplant. © 1995 Lippincott-Raven Publishers, Philadelphia

Macrophages in solid organ transplantation

Macrophages are highly plastic hematopoietic cells with diversified functions related to their anatomic location and differentiation states. A number of recent studies have examined the role of macrophages in solid organ transplantation. These studies show that macrophages can induce allograft injury but, conversely, can also promote tissue repair in ischemia-reperfusion injury and acute rejection. Therapeutic strategies that target macrophages to improve outcomes in solid organ transplant recipients are being examined in preclinical and clinical models. In this review, we discuss the role of macrophages in different types of injury and rejection, with a focus on macrophage-mediated tissue injury, specifically vascular injury, repair and remodeling. We also discuss emerging macrophage-centered therapeutic opportunities in solid organ transplantation

Biomarkers in solid organ transplantation: establishing personalized transplantation medicine.

Technological advances in molecular and in silico research have enabled significant progress towards personalized transplantation medicine. It is now possible to conduct comprehensive biomarker development studies of transplant organ pathologies, correlating genomic, transcriptomic and proteomic information from donor and recipient with clinical and histological phenotypes. Translation of these advances to the clinical setting will allow assessment of an individual patient's risk of allograft damage or accommodation. Transplantation biomarkers are needed for active monitoring of immunosuppression, to reduce patient morbidity, and to improve long-term allograft function and life expectancy. Here, we highlight recent pre- and post-transplantation biomarkers of acute and chronic allograft damage or adaptation, focusing on peripheral blood-based methodologies for non-invasive application. We then critically discuss current findings with respect to their future application in routine clinical transplantation medicine. Complement-system-associated SNPs present potential biomarkers that may be used to indicate the baseline risk for allograft damage prior to transplantation. The detection of antibodies against novel, non-HLA, MICA antigens, and the expression of cytokine genes and proteins and cytotoxicity-related genes have been correlated with allograft damage and are potential post-transplantation biomarkers indicating allograft damage at the molecular level, although these do not have clinical relevance yet. Several multi-gene expression-based biomarker panels have been identified that accurately predicted graft accommodation in liver transplant recipients and may be developed into a predictive biomarker assay

Usage of Tacrolimus and Mycophenolic Acid During Conception, Pregnancy, and Lactation, and Its Implications for Therapeutic Drug Monitoring: A Systematic Critical Review

BACKGROUND: Conception, pregnancy, and lactation following solid organ transplantation require appropriate management. The most frequently used immunosu

Anesthetic Considerations in Transplant Recipients for Nontransplant Surgery

As solid organ transplantation increases and patient survival improves, it will become more common for these patients to present for nontransplant surgery. Recipients may present with medical problems unique to the transplant, and important considerations are necessary to keep the transplanted organ functioning. A comprehensive preoperative examination with specific focus on graft functioning is required. The anesthesiologist needs to pay close attention to considerations of immunosuppressive regimens, blood product administration, drug interactions as well as the risk and benefits of invasive monitoring in these immunosuppressed patients. This article reviews the post-transplant physiology and anesthetic considerations for patients after solid organ transplantation