A new study has highlighted low-dose tacrolimus based regimes may be the best method to prevent rejection in kidney transplant recipients. The study was the largest of its sort comparing four different regimens for ongoing treatment following kidney transplantation. Results of the SYMPHONY trial were presented at the World Transplant Congress (WTC) in Boston, Massachusetts in July 2006, along with other new and exciting research in this field.
Organ transplantation refers to moving whole or part of an organ from one body to another, with the aim of replacing the function of a diseased organ. Organ transplantation has provided amazing revolutions in the field of medicine in the 20th century. In 1905 the first cornea (clear disk at the front of the eye) was successfully transplanted. Today patients with severe and life-threatening diseases can have various new healthy organs (including the kidneys, lung, liver, heart and pancreas) transplanted into their body. Depending on the situation, organs may be harvested from deceased or living donors that may or may not be related to the patient. Furthermore depending on the type of transplant, the defective organ may either be left in the body or be removed and replaced completely. In both instances the new organ acts to replace the functions of the defective organ. Despite these amazing advances, several challenges remain in the field of transplantation. The largest issue is the management of rejection. Our bodies have a sophisticated immune system developed to protect our bodies from nasty infections and diseases. This system has special mechanisms to identify the body’s own tissues as ‘self’ and to identify diseases and infections as ‘foreign.’ Unfortunately it is not easy to switch this system on and off! When an organ is transplanted into the body, the immune system identifies it as ‘foreign’ and attacks it like it would other diseases or infections. This process is referred to a rejection and can lead to failure of the transplanted organ. Following a transplant patients therefore need to take a whole range of medications to suppress their immune system called immunosuppressants. As you can imagine, these medications can have significant side effects as the immune system has less ability to fight infections and cancers. Therefore there needs to be a careful balance between preventing rejection and reducing toxicity. Numerous studies have been conducted in this field. Of particular interest has been the role of a class of medications called calcineurin inhibitors (such as tacrolimus and cyclosporin) in the prevention of kidney transplant rejections. A recent study called the SYMPHONY trial compared four different immunosuppressant regimens in renal transplant patients. Over 1600 patients were included in the trial from 15 different countries. Patients were randomly assigned to receive either the usual dose of cyclosporine, low dose sirolimus, low-dose cyclosporine or low dose tacrolimus in conjunction with other drugs such as steroids that also suppress the immune system. The four drugs investigated are all different types of immunosuppressant agents that are taken long-term after a transplant. Results of the SYMPHONY trial were presented at the renowned World Transplant Congress (WTC) in Boston in 2006. The main results were in favour of tacrolimus regimen which produced less rejection (damage to the transplant by the immune system) and less toxic side effects compared to the other treatments. Tacrolimus based regimens may therefore be the best method to prevent rejection. This study provides hopeful data suggesting that tacrolimus immunosuppressant regimens following renal transplant may produce better outcomes. This may help improve survival of the transplanted grafts and reduce side effects for transplant recipients. However further research is still needed as this study was only short (one year duration) and not all safety issues were considered. Many clinicians however already use this treatment. If you are undergoing a transplant, it is important that you discuss immunosuppressant options in detail with a specialist. (Kindly reviewed by Dr Dwarakanathan, MD DM FRCP FRACP, Senior Consultant Nephrologist at Royal Brisbane & Women’s Hospital and Editorial Advisory Board Member of the Virtual Renal Centre.)