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Background: Solid organ transplant centers are increasingly using induction immunosuppression strategies. Induction immunosuppression involves the use of intense therapy at the time of transplantation with the goal of preventing acute rejection and ultimately inducing a tolerogenic state. The objective of this review is to examine specialized induction agents currently in clinical use and highlight novel therapeutics on the horizon for induction immunosuppression., Methods: A literature search using the PubMed and MEDLINE databases identified salient basic science and clinical research articles on induction immunosuppression for solid organ transplantation., Conclusions: While current induction immunosuppression agents have reduced the incidence of acute rejection, the goal of transplant tolerance has not been realized. Furthermore, the long-term allograft survival rate is not clearly influenced by the practice of induction immunosuppression. New approaches to tolerance induction, such as costimulatory-based therapy, mixed chimerism, and adoptive cellular transfer, hold promise for more effective induction immunosuppression in solid organ transplantation.

We introduce a new concept of psychosocial profiling as a tool that provides the transplant team with a psychosocial framework for identification, intervention and management of non-compliance. This will also increase our understanding of emotional problems experienced by patients before transplant, as a result of living with the uncertainty and medical side effects of chronic illness. Psychosocial profiling is adaptable throughout the transplant process and gives every patient an opportunity of psychosocial support to help him or her into a position of emotional stability and compliance with their medications and postoperative care. Implementation of this strategy will move health care professionals from being gatekeepers to managers and facilitators of holistic care in recipients of transplants.

In the United Kingdom, people from the Indian subcontinent have a higher incidence of kidney failure, are less likely to receive a kidney transplant, and have a higher mortality rate from renal disease. In addition, Asians are reluctant donors; white people make up 95% of the donor pool. We developed a questionnaire to determine the knowledge and attitudes toward organ donation in the Asian communities. The setting was a public forum; the aims were (1) to study the attitudes of Asians toward organ donation, (2) to validate our questionnaire, and (3) to initiate a campaign of increasing awareness of organ donation and transplantation in the Asian community in the greater Glasgow area. Our survey suggested that Asians have an awareness of organ donation and transplantation, and they would donate an organ to a family member; however, they did not carry a donor card. Respondents unanimously agreed that lobbying by religious leaders was the best means to promote awareness.

The correction of post-transplant hyperlipidaemia warrants the judicious and timely use of pharmacological agents with dietary modification and exercise. Reduction in hyperlipidaemia may have some role in decreasing the incidence of chronic rejection of allografts. The awareness that the morbidity and mortality of atherosclerotic disease may be lowered by active intervention will result in a better quality of life for transplant recipients.

Immunosuppressive agents increase the risk of death due to coronary disease or stroke by their ability to cause 3 different adverse effects: dyslipidaemia, hypertension and hyperglycaemia. Post-transplant diabetes mellitus has emerged as a major adverse effect of immunosuppressants. As recipients of organ transplants survive longer, the secondary complications of diabetes mellitus have assumed greater importance. There is a need for a precise definition of post-transplant diabetes mellitus to facilitate inter-centre comparison and to study the natural history of post-transplant diabetes mellitus. We recommend broad criteria to define hyperglycaemia, as a fasting blood glucose level of > 400 mg/dl at any point or > 200 mg/dl for 2 weeks, or a need for insulin treatment for at least 2 weeks. We also recommend serial measurements of HbA1c. Cyclosporin and tacrolimus cause post-transplant diabetes mellitus by a number of mechanisms, including decreased insulin secretion, increased insulin resistance or a direct toxic effect on the beta cell. For corticosteroids, the induction of insulin resistance seems to be the predominant factor. However, few studies have examined the mechanism of diabetogenicity at the molecular level. This may hold the key for pharmacological manipulation of current immunosuppressive regimens which may result in decreased metabolic complications. Corticosteroid sparing regimens have been shown to reduce the metabolic complications of immunosuppressants including post-transplant diabetes mellitus. However, their use should be balanced against the increased incidence of transplant rejections. Post-transplant diabetes mellitus may be organ-specific irrespective of the immunosuppressant used. Tacrolimus causes a high incidence of post-transplant diabetes mellitus in recipients of kidney transplants (upto 20% in some reports); the diabetogenicity of cyclosporin-based regimens is comparable with that of tacrolimus-based regimens in recipients of liver transplants. A few clinical studies in which attempts were made to discontinue cyclosporin resulted in an unacceptable loss of the transplant. In the case of tacrolimus, complete withdrawal of immunosuppression may be possible in selected patients with liver transplants. However, post-transplant recipients who may benefit from this approach are difficult to identify. In some early series, patients received doses of tacrolimus that were approximately 2 to 3 times higher than those currently used, which may have resulted in a higher incidence of post-transplant diabetes mellitus. More recently, it has been shown that tacrolimus was successful in salvaging whole pancreatic grafts which were maintained on cyclosporin. Tacrolimus-based immunosuppression as primary therapy was also used with remarkable success in solitary whole pancreas transplants. Strategies to reduce the metabolic complications of immunosuppressants should be pursued aggressively as this will directly lead to a decrease in long term cardiovascular adverse effects.

A new hypothesis has been proposed which states that microchimerism is the basis for the clinical tolerance seen in long-term survivors of solid organ transplants. Efforts to enhance microchimerism include simultaneous infusion of bone marrow of donor origin and transplantation of a solid organ. Studies are in progress to verify the phenomenon of microchimerism and its role in clinical tolerance.