Kidney/Pancreas/Islet Transplant Research
Mayo Clinic Rochester carries out over 250 kidney and pancreas transplants each year as treatment for kidney failure and complications of diabetes. In addition, a new clinical program for transplantation of pancreatic islets in diabetic patients is currently in development.
The central themes of the Kidney/Pancreas/Islet Transplant Program at Mayo Clinic Rochester are:
- To provide the highest level of care to transplant candidates, transplant recipients, and living kidney donors.
- To advance the science of transplantation in order to overcome existing barriers to immediate and long-term transplant success.
The program maintains active research initiatives in both clinical and laboratory investigations that are funded from NIH grants as well as from other governmental agencies, industry support, private funding and intramural sources. Below is a listing of several of the current research areas within the program that have been the subject of multiple peer-reviewed publications over the past five years.
Kidney transplantation across blood group and positive cross-match barriers
Kidney transplantation is usually not performed if the potential donor has a different blood type to the recipient or if the recipient is shown to have pre-existing antibodies that recognized donor cells (a "positive cross-match"). In these circumstances there is a high risk that the transplanted kidney would be quickly destroyed as a result of binding of antibody.
Researchers at Mayo Clinic Rochester have been among the first to development treatment strategies for reducing antibody levels and achieving successful living donor kidney transplantation despite different blood groups or a positive cross-match. The success of these strategies has allowed individuals with kidney failure to avoid lengthy or indefinite waiting periods for deceased donor transplants.
This clinical initiative has developed into the largest such program in the United States with over 50 blood group incompatible/positive cross-match transplants carried out to date.
Ongoing research in this area includes:
- studies of the effect of antibody development after transplantation on graft function
- laboratory investigations of the cells responsible for production of damaging antibodies
- clinical testing of new treatments for lowering or preventing the production of donor-specific antibodies
Long-term kidney transplant function and chronic injury to kidney transplants
Many kidney transplants fail over time because of the gradual development of scarring (chronic fibrosis) despite careful management of anti-rejection treatment. This process, the causes of which are not completely understood, represents one of the most important challenges to the success of kidney transplantation.
Mayo Clinic Rochester researchers have developed a number of resources and projects in order to study chronic fibrosis among kidney transplant recipients and, eventually, to find ways of preventing or treating it. These include:
- a continually updated database that allows transplant function to be carefully followed over time in thousands of patients
- pathology studies of kidney transplants at specific time points during the first five years after surgery
- microarray studies examining the expression of thousands of genes within kidney transplant tissues
- screening tests for potentially damaging viral infections and immune responses in kidney transplant recipients
The living kidney donor
Mayo Clinic Rochester has carried out living donor kidney transplantation since 1963 and is currently the largest single living donor program in the United States. In order for the practice of living donor transplantation to remain successful and be carried out safely for both donor and recipient, Mayo Clinic researchers have placed a high priority on research into the short and long-term outcomes from kidney donation. Ongoing clinical investigations:
- effect of kidney donation on blood pressure
- impact of obesity on kidney donation
- long-term outcomes of kidney donation
- impact of donor age on transplant success
Immunosuppression for kidney and pancreas transplantation
As new anti-rejection (immunosuppressive) medications are developed, their potential to improve overall outcomes from transplantation in some or all patients must be carefully evaluated. Because most organ transplants require the use of two or more medications combined over time, there is a growing complexity to the design of optimal immunosuppression regimens for individual organs and patient groups.
The Kidney/Pancreas/Islet Transplant Program at Mayo Clinic Rochester has carried out or participated in many clinical studies designed to examine the benefits associated with new immunosuppressive medications and combinations of medications compared to established regimens. These studies provide essential information to shape future treatment models as well as serving as a basis for laboratory studies of the molecular features of transplanted organs under different circumstances. An example of this research is an ongoing randomized, controlled clinical trial comparing the safety and long-term effectiveness of two classes of primary antirejection medication - the calcineurin inhibitor tacrolimus and the mTOR inhibitor, sirolimus.
Cardiovascular complications, diabetes, obesity in kidney transplant recipients
Many recipients of kidney transplants are at high risk for cardiovascular complications such as heart attack, stroke, and loss of blood supply to the limbs as a result of underlying medical diseases as well as medication-related toxicities. For many of these patients, the combination of obesity, abnormal lipid levels, and abnormal blood sugar metabolism can be identified before or soon after the transplant and related to subsequent cardiovascular events.
Research into the causes for cardiovascular disease in transplant recipients and the benefits of different treatment/prevention strategies has the potential to prolong the lives of many patients. Research studies using database information from thousands of kidney transplant recipients at Mayo Clinic as well as clinical trials of intervention for cardiovascular risk factors are currently being carried out with the goal of developing comprehensive models for predicting and preventing cardiovascular events in the future.