Long-Term Outcomes Project

A major project of the Transplant Immunology Program is designing clinical trials to improve long-term outcomes for transplant patients, a major unmet need in the area of transplantation.

The overall goal of the Long-Term Outcomes Project is to ensure that every patient who needs a transplant receives one, and that the transplanted organ lasts a lifetime. The scientific goal of the project is to better understand how the immune system interacts with the graft — a multifactorial process characterized by progressive decline in function and premature graft loss.

Since the early 2000s, the kidney transplant team has championed the use of "surveillance" renal allograft biopsies, in which functional kidneys are tested at multiple times post-transplant (four months and one, two, five and 10 years). The surveillance kidneys are also paired with a variety of clinical laboratory test data, including graft function, donor-specific antibody, polyoma virus, and so on.

Thousands of biopsies have been analyzed using traditional light microscopy to identify immune and nonimmune causes of graft injury early on — before the graft is irreversibly damaged. Further analyses using gene expression profiling have been used to understand the intragraft characteristics of specific histologic findings.

Through these kidney biopsy studies, several intragraft characteristics have been identified that are associated with future graft loss, and which are likely present in other solid-organ transplants. Two of the most deleterious are lesions related to antibody-mediated injury and increased immune cell inflammation. Early identification of patients affected by these processes allows for designing specific therapy to potentially manage or reverse them.

The intent of the Transplant Immunology Program's Long-Term Outcomes Project is to:

  • Develop and implement specific protocols for routine patient follow-up
  • Use the information obtained from these protocols (labs, biopsies, and so on) to identify the individual patients to include in targeted clinical trials with existing or new therapeutic interventions

By performing clinical trials with patients at the highest risk and with more homogenous phenotypes, the effect of the intervention can be more carefully explored.

Areas of focus

Ongoing research in the Long-Term Outcome Project includes:

  • Redesigning clinical trials, including the use of surrogate endpoints and biomarkers using new investigative approaches
  • Conducting surveillance biopsies
  • Overcoming antibody barriers to successful transplants
  • Increasing follow-up appointment compliance to assess organ function, histology and donor-specific antibodies
  • Working with a consortium of other centers and pharmaceutical companies to accelerate the study of more patients and validate results

Outcomes

By improving long-term graft survival, our research ensures that patients have improved quality of life and are less likely to require second transplants during their lifetimes.

Please contact us for more information about long-term outcomes research in the Transplant Immunology Program at Mayo Clinic.