Complications of Post-Transplant Immunosuppression
Transplantation is one of the revolutionary fields in modern medicine that has saved thousands of lives. The continuous refinement of surgical techniques and the availability of potent immunosuppressive drugs have made transplantation the most effective treatment option for patients with end stage organ failure. Over 25 000 organ transplants are performed in the USA each year and survival rates following transplantation are now approaching 90% at 1 year and 75% at 5 years, depending on the organ transplant (kidney, liver, pancreas, heart, lung, intestine). Central to this success was the introduction of drugs that suppress the immune system and prevent rejection. Indeed, across organs, the use of current immunosuppression regimens effectively prevents acute rejection in the majority of patients. As a result, the incidence of graft loss due to acute rejection has decreased dramatically compared to the early era of transplantation. This success of organ transplantation has led to a growing population of immunosuppressed transplant recipients with prolonged survival with a functioning graft, but also with prolonged exposure to the side effects and complications of chronic immunosuppression. Indeed, the burden of chronic immunosuppression post-transplant has become a growing concern among transplant physicians, although its impact is currently smaller compared to two decades ago, following the introduction of new and less-toxic immunosuppression regimens (see below). However, chronic immunosuppression remains associated with significant morbidity: as an example, the majority of patients treated with calcineurin inhibitors develop some degree of renal function impairment and up to 10% progress to kidney failure requiring dialysis or kidney transplant (see below). The consequences of chronic immunosuppression on multiple organ systems are becoming increasingly evident and often new symptoms or disorders develop post-transplant as a consequence of the side-effects of immunosuppressive drugs (ie opportunistic infections, malignancies, diabetes mellitus, hypertension and others, see below). The onset of new post-transplant conditions requiring treatment has multiple implications in terms of function of the graft, patient compliance and cost. Therefore, strategies to limit and prevent the complications of prolonged immunosuppression post-transplant are needed. Here we present briefly the most common immunosuppression regimens currently used in abdominal organ transplantation and we review current major complications and challenges of prolonged immunosuppression after transplant. We will discuss issues common to abdominal organ transplants including liver, intestine, pancreas, kidney, without entering into organ-specific issues. The discussion is limited to adult transplant recipients, since pediatric transplantation raises a number of issues specific to this age group in terms of immunosuppression regimens and its complications including growth-related issues and compliance. In addition, a pediatric transplant recipient has potentially an expected more prolonged exposure to chronic immunosuppression than an adult and, as a consequence, more time to develop complications. We will also present current strategies in the management of complications of immunosuppression and ways to limit the burden of immunosuppression. Finally, we report on current research and indicate future directions to improve post-transplant immunosuppression.