Trial Information

Immune Development and Alloimmunity in Pediatric Renal Transplant Recipients

Over the past forty years, the use of increasingly effective immunosuppressive drugs has
decreased the risk for organ rejection (acute rejection, AR) considerably, and improved
short-term outcomes. However, these costly and complicated life-long treatment regimens also
cause serious complications in the long-term.

While transplant recipients live significantly longer lives than patients on dialysis,
transplant recipients still have much shorter life spans than their healthy counterparts.
Among reasons for this difference in life-expectancy are the immunosuppressive-drug related
side effects that can lead to complications such as life threatening infections,
malignancies, high blood pressure, heart disease, and diabetes. Additionally, certain drugs
used to prevent organ rejection are known to contribute to renal damage, leading many
patients to experience graft loss within 15 years. To that end, many children undergoing
successful kidney transplantation require re-transplantation as adults. Therefore, while
transplantation yields high success rates in the short-term, the drugs that are responsible
for this early and temporary success are also the cause of later, serious complications.
This is especially true for children, who endure extended drug exposures.

The purpose of this study is to explore the impact of viral exposure on children who receive
immunosuppressive medications after renal transplantation; study the cellular changes
associated with these influences; monitor medication adherence; and observe how all these
factors affect the outcome of kidney transplantation in children. The hope is to better
understand these processes to optimize future transplant therapies for the pediatric
transplant recipient.

This study is designed to observe the immune system response during the first year after
kidney transplant. Cells of the immune system in the recipient's blood, urine, and
transplanted kidney will be tested to observe how the drugs used to prevent rejection
influence them, if these cells change over time, and if they are related to kidney
rejection. The comparisons will allow researchers to study how the developing immune system
interacts with the kidney transplant. Blood from the kidney donor will be requested so
that researchers can study how the recipient's immune system interacts with donor cells.

This study will also look closely at how well participants take prescribed medications.
Since transplant medications are known to change the immune system, tests of the immune
system cells will be compared to tests designed to measure how accurately medications are
taken. Medication adherence will be measured using electronic medication bottle cap records,
paper survey results, and drug levels in the blood. In this way, the study team hopes to
learn about the impact of children's medications on their immune system.

This study will take place at multiple transplant centers in the United States. It is
observational and will involve approximately 75 pediatric renal participants. The study will
last for a total of 3 years, which includes a 2 year accrual period and 12 month follow up.
Clinical treatment will be determined by standard of care at each participating center.
There will be Baseline assessments which will occur before and on the day of transplantation
and follow-up study visits will take place at months 1, 3, 6, 9, and 12 after transplant.
Study assessments and specimens will also be collected at the time of each clinically
indicated biopsy. Study assessments during these follow-up visits will include vital signs;
review of current medications; questions related to adverse events (infection, rejection,
graft failure, malignancy); treatment adherence surveys; and specimen collection for local
and central laboratory testing.