Focus on Transplantation

This edition of The Immunology Report focuses on the detection and prevention of antibody-mediated rejection; new immunosuppressants for use in renal transplant recipients; the impact of Risk Evaluation and Mitigation Strategies (REMS) on immunosuppressive therapy; and long-term management of primary care issues—including malignancy, infection, hypertension, and diabetes—in the transplant population.

VIEW Report
Dixon B. Kaufman, MD, PhD
Dixon B. Kaufman, MD, PhD

Organ transplantation represents one of the great achievements of modern medicine in the last half of the 20th Century. Advances continue to be accomplished through the multidisciplinary approach to transplant patient care. Members of a multidisciplinary team must evaluate a transplant candidate’s physical condition, prepare that patient to receive and accept a foreign organ, surgically graft the donated organ into the recipient’s body, and then follow the transplant patient for life to ensure the health of both the graft and the recipient. An enormous wealth of information emerging from the laboratory and the clinic provides transplant teams with a more complete picture of the successes and risks inherent in the organ transplantation process.

The articles in this edition of The Immunology Report are based upon clinical and scientific presentations delivered during the 2012 American Transplant Congress, the joint annual meeting of the American Society of Transplant Surgeons and the American Society of Transplantation, held June 2–6, 2012, in Boston, Massachusetts. Transplant surgeons, physicians, scientists, immunologists, and nephrologists were privy to the results of pivotal clinical trials and theories on physiologic pathways, optimal immunosuppressive regimens, postsurgical followup, and other aspects of patient care. The authors, all first beginning their careers in transplant medicine and surgery, attended a number of these scientific sessions to share important information on trends in transplantation and immunosuppression.

Antibody-mediated rejection (AMR) is a challenging issue impeding progress toward the attainment of long-term survival in kidney transplant recipients. Stephen H. Gray, MD, MsPH, from the University of Alabama at Birmingham, describes the immunologic pathways that may lead to AMR. In addition, he reviews current information on diagnostic criteria and markers of AMR, tests that can detect rejection early, and drug therapy that may be tried to prevent rejection and allow renal allografts to survive for prolonged periods. In addition, Dr. Gray relates information about the monitoring of antibodies in sensitized and unsensitized recipients of kidney transplants.

Tried-and-true immunosuppressive regimens save both donated organs and the lives of their recipients, but they also have serious adverse effects—and they can fail transplant patients. Phillip S. Weems, MD, from the University of Wisconsin School of Medicine and Public Health, reviews the advantages and disadvantages of various immunosuppressants, including calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, monoclonal antibody fusion proteins, Janus kinases, and novel biologic agents currently being evaluated in phase I/II trials to suppress the immune systems of transplant patients. In particular, he discusses the pros and cons of several immunosuppressant drug combinations and the clinical implications of switching renal transplant patients from calcineurin inhibitors to mTOR inhibitors.

Even after the US Food and Drug Administration (FDA) approves the marketing of a new drug, its safety continues to be closely scrutinized. Satish N. Nadig, MD, DPhil, from the University of Michigan Medical School in Ann Arbor, offers an abbreviated history of the health crises that lead to present drug regulatory practices in the United States and then describes the current demands imposed by Risk Evaluation and Mitigation Strategies (REMS) on the transplantation community. As of 2007, REMS provide materials to inform patients about the serious risks related to using a drug, to minimize the chance that such a drug might interact adversely with another drug or disease entity, and to prevent the risk of fetal exposure to potentially teratogenic agents. In addition, they represent a means to accomplish postmarketing surveillance of these pharmaceuticals. This article reviews various components of REMS, duties that these strategies require from healthcare personnel and patients, and specific REMS associated with currently used immunosuppressants.

Care of the transplant patient hardly ends with implantation of a donated organ. Postoperative management of transplant patients is complicated and risky. Jared Brandenberger, MD, from the University of Washington Medical Center in Seattle, reviews primary care issues that may threaten the health of a graft and, ultimately, the patient. Topics covered in his article include the management of diabetes mellitus and hypertension in the transplant population. In addition, Dr. Brandenberger details methods to prevent infection following organ transplant and to screen transplant recipients for malignancies.

The authors of this report have done a great service by sharing expert insights on a variety of topics of vital interest to the transplantation community. We thank them for their efforts and look forward to groundbreaking results of clinical trials and more data on the safety and efficacy of novel therapeutics now being tested.

Dr. Kaufman is Ray D. Owen Professor of Surgery and Chairman, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Astellas Pharma US, Inc.
Supported by an educational grant from Astellas Pharma US, Inc.