Purpose:
The purpose of this study is to examine the effects of withdrawing steroids on graft
rejection and kidney functions in kidney transplant recipients between the ages of 0 and 20
years (prior to their 21st birthday).
Graft survival has improved in recent years in children with kidney transplants. One bad
side effect of steroid maintenance therapy has been growth retardation. Doctors believe
steroids might be safely withdrawn in patients that are receiving other maintenance
therapies. If steroids are removed, children might catch up in their growth and also might
have fewer side effects of other kinds. This study evaluates whether steroid therapy can be
withdrawn in a way that does not increase graft rejection.
Study summary:
Children receiving kidney (renal) transplantation face distressing issues in
post-transplantation including but not limited to growth retardation directly attributable
to corticosteroids (steroids). It is hypothesized that robust immunosuppression with
sirolimus and calcineurin inhibitors (cyclosporine or tacrolimus) in conjunction with
induction therapy should enable successful steroid withdrawal. A steroid-free environment
could lessen side effects by enabling a child to achieve catch-up growth, reducing the need
for anti-hypertensive therapy, and reducing the risk of cardiovascular disease. This trial
tests the objective of providing a steroid-free state without incurring the risk of
increased incidence of acute transplant rejections.
Patients are enrolled prior to kidney transplantation and receive standard evaluations.
Patients receive induction therapy with basiliximab preoperatively and on Day 4 after
surgery. Immunosuppressive therapy begins with sirolimus and either cyclosporine or
tacrolimus on Day 1 following surgery, and with corticosteroids the day of surgery.
Infection prophylaxis with Bactrim is begun on Day 1 after surgery and center-specific
anti-cytomegalovirus (CMV) therapy is given for all recipients of a CMV positive kidney. At
6 months post-transplantation, all patients who have not had an episode of acute rejection
undergo a renal graft biopsy. Patients who are confirmed to be free of subclinical rejection
are randomized to either undergo complete steroid withdrawal or continue maintenance on
daily steroids. Patients receive either steroids or placebo, while continuing other
immunosuppressive medications. Patients are segregated into weight groups for steroid
withdrawal that occurs over months 7 to 13. Any acute rejection event during withdrawal is
confirmed by renal biopsy and managed with methylprednisolone treatment. Patients are
followed for 3 years post-transplantation for analysis of growth rate, blood pressure, lipid
profile and renal function as measured by serum creatinine and calculated creatinine
clearances. Post-transplantation clinic visits are weekly for the first 2 months, every 2
weeks until 13 months, weekly during Month 13, every 2 weeks through Month 18, and monthly
until the study ends.
Patients who exhibit evidence of acute or subclinical rejection do not continue the steroid
withdrawal trial and care is managed by their pediatric renal transplant center physicians.
Criteria:
Inclusion Criteria:
Patients may be eligible for this study if they:
- Are between the ages of 0 and 20 years (prior to their 21st birthday)
- Are receiving their first living related (e.g.,kidney from a relative or unrelated
donor) or cadaver donor transplant
- Are willing to practice an acceptable method of birth control during the study, if
women able to have children
Exclusion Criteria:
Patients will not be eligible for this study if they:
- Have received multiple organs
- Have received 2 or more transplants
- Have an active infection (including tuberculosis), or cancer
- Have used an experimental agent within 4 weeks of transplantation