Kidney and Pancreas Transplant Research Program
The Kidney and Pancreas Transplant Research Program within the Mayo Clinic Transplant Research Center focuses its research efforts on overcoming the challenges that limit the success of kidney and pancreas transplantation.
Research focus areas
Research focus areas in the Kidney and Pancreas Transplant Research Program include:
- Overcoming antibody barriers
- Reducing disease recurrence
- Improving long-term success
- Expanding living-donor transplants
- Pre-emptive transplantation
- Immunosuppression characteristics and new treatments
- Managing cardiovascular complications
Here's a closer look at the focus areas.
Overcoming antibody barriers
Researchers in the Kidney and Pancreas Transplant Research Program have led the way in developing treatment strategies that reduce antibody levels, which allowed for successful living-donor kidney transplants even with incompatible blood types.
Antibodies are proteins produced by the body to protect it against substances, cells or organs that are foreign. These antibodies are essential for health. However, at times these antibodies can prevent a patient from receiving a transplant, because they can quickly destroy the transplanted kidney or pancreas. Antibodies can be directed against blood groups or against donor cells (called a positive crossmatch).
Researchers have developed several strategies to allow transplantation even in the presence of antibodies.
- At Mayo Clinic, investigators apply sophisticated techniques to differentiate which antibodies pose a problem for transplantation and which don't.
- Researchers also apply techniques to remove these antibodies from blood before transplant and to control negative effects of these antibodies on the kidney with medications.
- Patients with kidney failure and high levels of antibodies can receive kidneys from a larger pool of living donors and may be able to participate in Mayo Clinic's paired donation program. As a result, qualified patients with kidney failure are able to avoid lengthy or indefinite waiting periods for deceased-donor transplants.
Ongoing research in the area of antibody resistance includes:
- The effect of antibody development on the transplanted kidney and pancreas
- Laboratory investigations of the cells responsible for producing damaging antibodies
- Clinical testing of new treatments for reducing or preventing the production of donor-specific antibodies
Reducing disease recurrence
Researchers in the Kidney and Pancreas Transplant Research Program are studying ways to identify treatments that reduce the risk of recurrent disease after a kidney transplant.
Several of the diseases that can cause kidney failure can come back and attack a newly transplanted kidney. In fact, approximately 20% to 25% of kidney transplants are lost because of disease recurrence.
To address this problem, Mayo Clinic researchers have taken several steps.
- First, researchers identified diseases that are most likely to recur in the transplanted kidney.
- Second, with the use of protocol biopsies, researchers identified the earliest signs of disease recurrence in the transplanted kidney, with the intent of improving outcomes by treating patients when disease recurrence is detected.
- Third, researchers developed new treatments that can be given to the patient to prevent disease recurrence or to treat it when it occurs.
Researchers have made significant advances in the prevention and treatment of some of the most dangerous diseases for the transplanted kidney, including focal segmental glomerulosclerosis, membranous nephropathy and membranoproliferative glomerulonephritis.
Research in this area continues to further refine disease classification and identify optimal treatment options to prevent disease recurrence because each of these diseases seems to require specific management strategies.
Improving long-term success
The premature loss of transplanted organs traditionally has been attributed to poorly characterized diseases that are frequently lumped together under the term "chronic rejection."
Researchers in the Kidney and Pancreas Transplant Research Program have taken a different approach to this problem by first questioning what precisely causes the loss of kidney and pancreas transplants.
Using kidney biopsies and careful examination of laboratory and clinical parameters, the Mayo Clinic researchers determined that kidney transplants can be lost for multiple reasons. In most cases, the cause of the kidney loss was because of known diseases that could potentially be prevented and treated.
These investigations also make it abundantly clear that a comprehensive approach addressing all the threats that can harm the transplanted organ is needed for transplant success.
Researchers developed a series of tools that allow them to monitor outcomes-particular management strategies.
These tools include:
- A continually updated database to gather information about a multitude of clinical, laboratory and biopsy parameters in thousands of patients over time
- Protocol biopsies for pathology review of kidney transplants at specific time points during the first 10 years after transplant
- Microarray studies examining the expression of thousands of genes within kidney transplant tissues, helping researchers understand how the kidney reacts in response to injury
- Screening tests for potentially damaging viral infections and immune responses in kidney transplant recipients
- Monitoring of the production of antibodies against the transplanted kidney or pancreas, thus allowing researchers to determine whether immunosuppressive medications that the patient receives after the transplant are effective
Expanding living-donor transplants
Mayo Clinic has performed living-donor kidney transplants since 1963 and has the largest single-living-donor program in the United States.
In order for the practice of living-donor transplant to remain successful and safe for both donor and recipient, researchers in the Kidney and Pancreas Transplant Research Program have placed a high priority on research into the short- and long-term outcomes for kidney donation.
Ongoing clinical investigations include:
- 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
Researchers in the Kidney and Pancreas Transplant Research Program also have a strong commitment to expand pre-emptive transplantation — transplantation of a kidney in patients who have never received dialysis.
Investigators have shown in the past that dialysis prior to transplantation limits the life span of the recipient. Avoiding dialysis, particularly for more than one year, has beneficial consequences for the patient and perhaps the transplanted organ. In addition, pre-emptive transplantation reduces medical costs.
At times, patients are told that a period of dialysis is required before receiving a transplant. Researchers at Mayo Clinic believe that patients should be encouraged to consider transplantation as their kidneys start to fail.
The success of this program is closely tied to the success of living-donor kidney transplantation in the Kidney and Pancreas Transplant Research Program. However, it's possible to achieve pre-emptive transplantation with deceased-donor kidneys if patients are placed on the waiting list soon enough.
Ongoing investigations include:
- Evaluation of medical, psychological, quality of life and financial implications of pre-emptive transplantation
- Evaluation on how collaborative efforts with referring physicians and even insurance companies can facilitate pre-emptive transplantation
Immunosuppression characteristics and new treatments
The Kidney and Pancreas Transplant Research Program has conducted and participated in many clinical studies designed to examine the benefits associated with new immunosuppressive medications and combinations of medications compared with established regimens.
Because most organ transplants require the use of two or more medications combined over time, the design of optimal immunosuppression regimens for individual organs and patient groups has grown more complex.
Mayo Clinic researchers have examined changes in the structure of transplanted kidneys using protocol biopsies and determined that prolongation of kidney survival likely will require re-examination of the approach to immunosuppression after the first year post-transplant.
By understanding what is happening inside the transplanted organ, researchers can design new strategies to achieve long-term success. Protocol biopsies are essential tools to achieve this goal.
Managing cardiovascular complications
Mayo Clinic researchers and physicians are conducting research to identify the causes of cardiovascular disease in kidney transplant recipients and the benefits of different treatment and prevention strategies.
Certain kidney transplant recipients are at higher risk of developing cardiovascular complications, such as heart attack, stroke and loss of blood supply to the limbs, typically from underlying medical diseases and medication-related toxicities.
Research studies using database information and measuring heart biomarkers in thousands of kidney transplant recipients at Mayo Clinic have improved the ability to identify patients who are at risk of heart problems after transplant
Investigators have found that the biomarker troponin levels can provide a more accurate measure of cardiac risk than can traditional cardiac measurements, such as a cardiac stress test, and can indicate whether surgical intervention is needed prior to kidney transplant.
The goals of this research are to achieve lower risk for patients and to conduct cardiac studies for patients who can benefit the most.
Ongoing studies include:
- Determining whether troponin can also be used to assess heart status after kidney or pancreas transplant
- Assessing how modifications in the treatment of patients before the transplant can reduce levels of troponin and perhaps reduce risk
Here's a list of faculty in the Kidney and Pancreas Transplant Research Program by campus location.
- Chakkera, Harini, M.D.
- Heilman, Raymond L., M.D.
- Huskey, Janna L. M.D.
- Khamash, Hasan A, M.D.
- Larsen, Brandon T., M.D., Ph.D.
- Mathur, Amit K., M.D.
- Morales, Alejandro, M.D.
- Moss, Adyr A., M.D.
- Petrides, Savas, M.D.
- Reddy, Kunam S., M.B.B.S.
- Singer, Andrew L., M.D., Ph.D.
- Sukumaran, Sumi Nair, M.B.B.S.
- Croome, Kristopher (Kris) P., M.D.
- Mai, Martin L., M.D.
- Oshel, Katherine, M.D.
- Perry, Dana K., M.D.
- Prendergast, Mary B., M.D.
- Taner, Burcin C., M.D.
- Wadei, Hani M., M.D.
- Amer, Hatem, M.D.
- Cosio, Fernando G., M.D.
- Cramer, Carl H. II., M.D.
- Dean, Patrick G., M.D.
- Heimbach, Julie K., M.D.
- Hickson, LaTonya J., M.D.
- Issa, Naim S., M.D.
- Kudva, Yogish C., M.B.B.S.
- Kukla, Aleksandra M.D.
- Lorenz, Elizabeth C., M.D.
- Norby, Suzanne M., M.D.
- Nyberg, Scott M.D., Ph.D.
- Prieto, Mikel, M.D.
- Schinstock, Carrie A., M.D.
- Schwab, Thomas R., M.D.
- Taler, Sandra J., M.D.
- Textor, Stephen C., M.D.