Induction therapy in pancreas transplantation

Abstract

Summary Induction therapy, the initial high‐dose bolus of immunosuppression given perioperatively to transplant patients, is almost ubiquitous in pancreas transplantation. Despite the frequent use, scientific data on the risks and benefits of induction therapy are scarce, especially as it concerns use specifically for pancreas transplantation. Indeed, none of the currently used induction agents are approved as induction therapy for pancreas transplantation, yet potential benefit is largely extrapolated from trials in kidney transplant recipients. This review summarizes which induction therapy agents are available both now and historically, their mechanisms of action, and provides an overview of the published literature describing the use of these agents in simultaneous pancreas–kidney transplant and solitary pancreas transplant recipients. In summary, there are two multicenter randomized trials, several single‐center randomized trials, and many other single‐center descriptive reports. Overall, the main benefit of induction therapy is the ability to wean steroids earlier, and the main downside is a higher risk of opportunistic infections. Despite a lack of solid evidence, over 90% of pancreas transplants performed annually in the United States receive some type of induction immunosuppression.

Tyrosine-Phosphatase and Glutamate-Decarboxylase Antibodies After Simultaneous Pancreas Kidney Transplantation: Do They Have an Impact on Pancreas Graft Survival?

“…This may support the use of induction therapies (IT), a standard protocol worldwide [6,18]. However, it has not been demonstrated that there is a clear benefit (any drug over another) on long-term outcomes or even that these auto-antibodies may play a role in outcomes [17,18].…”

“…It has been shown how pancreas transplantation may induce higher rates of rejection early after transplantation compared with liver or kidney transplantation alone (KTA) [17]. There are some articles in which it is suggested that autoantibodies (anti-GAD mainly) may be related at least in part with this phenomena.…”

The current challenges for pancreas transplantation for diabetes mellitus

“…As a consequence immunosuppressive practice has reflected practice in other areas of organ transplantation, with an additional effort to avoid prolonged steroid administration. Avoidance of steroids has been facilitated in part by the use of induction therapy, a short period of high dose immunosuppression in the peri-operative period, often characterised by the use of lymphocyte depleting antibodies [83].…”

Pancreas Transplantation: Solid Organ and Islet

“…The majority of units use biological induction (thymoglobulin, alemtuzumab, or basiliximab) followed by a combination of tacrolimus and mycophenolate, and the use of steroids is advocated by some but not all units. There is no conclusive evidence regarding optimal induction therapy; single center studies are small, and of the two multicenter trials, the largest examined an agent (daclizumab) that is no longer available, and the other used variable induction agents (Niederhaus et al 2013). The use of non-nephrotoxic medication is attractive, but experience in the use of sirolimus following pancreas transplantation remains limited (Kandula et al 2012).…”