Long-Term Outcomes Project

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

The overall goal of this project on long-term outcomes 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 that is often characterized by progressive decline in function and premature graft loss.

Since the early 2000s, our kidney transplant team has championed the use of surveillance renal allograft biopsies, in which functional kidneys are tested at multiple times post-transplant — first at four months and then at 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 and polyoma virus.

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. Additional 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 that are likely present in other solid organ transplants. Two of the most problematic 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 this research project is to:

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

Improving long-term graft survival can help patients have improved quality of life and reduce the need for a second transplant.