Immune Development in Pediatric Transplantation (IMPACT)
Condition: Chronic Kidney Failure; End Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
Study type: Observational

Summary: 
      Transplantation is the preferred method of treatment for end-stage renal disease (ESRD) in
      children. Over the past forty years, the use of newer immunosuppressive drugs has decreased
      the risk for organ rejection considerably, and improved short-term outcomes. However, these
      costly and complicated life-long treatment regimens also cause serious side effects. This has
      been particularly true for children, who undergo treatment with these drugs at the same time
      they are transitioning, physically and emotionally, from childhood to adulthood. These
      factors lead to significantly reduced life-spans, decreased drug regimen adherence, and an
      increased need for re-transplantation, as compared with adults.

      Current immunosuppressive procedures and strategies for children mimic those for adults,
      despite the difference between the two populations' immune systems and needs. New strategies
      aimed at tailoring to an individual child's needs would both reduce the risk of complications
      and improve outcomes. The purpose of this study is to generate information which will help to
      change the current practice of pediatric transplantation into one that is more individualized
      and preventative.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pediatric end-stage renal disease patients needing a kidney transplant
      
Keywords: Transplantation; Kidney Failure; End Stage Renal Disease; Pediatric