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.