Long-Term Outcomes Project

One of our major research projects is designing clinical trials that improve long-term outcomes for people who have undergone transplants.

The overall goal of this project is to ensure that every person 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. This interaction involves multiple factors in a process that is often characterized by progressive decline in function and premature graft loss.

Our kidney transplant team has championed the use of surveillance renal allograft biopsies since the early 2000s. These biopsies test functional kidneys posttransplant at four months and at one, two, five and 10 years. The surveillance kidneys also are paired with a variety of clinical laboratory test data, including graft function, donor-specific antibody and polyoma virus.

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

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

The intent of this research project is to:

  • Develop and implement specific protocols for routine follow-up of transplant recipients.
  • Use the information obtained from these protocols, such as lab work and biopsies, to identify individuals to include in targeted clinical trials for existing or new therapeutic interventions.
  • Conduct clinical trials with people at the highest risk and with more homogenous phenotypes so that the effects of the interventions can be more carefully explored.

Focus areas

Ongoing research in this project includes:

  • Redesigning clinical trials, including using surrogate endpoints and biomarkers with 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 people and validate results.

Outcomes

Improving long-term graft survival can give transplant recipients a better quality of life and reduce the need for a second transplant.