The purpose of this study is to see the effect of using drugs other than calcineurin
inhibitors to improve the rate of kidney transplant failure.
Kidney transplantation can help children with end-stage kidney disease. However, it has been
difficult to find treatment for donor graft rejection that does not have a lot of side
effects. Researchers hope to find treatments (immunosuppressants) with fewer side effects.
One approach is to avoid using calcineurin inhibitors and to try a new drug known as
sirolimus instead. Another is to use steroids less often. This study will test whether using
sirolimus, fewer steroid treatments, MMF, and certain antibodies will improve long-term
graft survival in children receiving kidney transplants from living donors.
Renal transplantation is widely recognized as the treatment of choice for children with
end-stage renal disease (ESRD). Although outcomes of renal transplantation in children have
improved during the past decade, success has been limited by both non-specific tolerance and
the complications associated with immunosuppressants. Steroids and calcineurin inhibitors
have the most toxic side effects. Use of sirolimus for immunosuppression has not been
associated with as many complications. Recent studies from Europe have demonstrated that
sirolimus can be combined with MMF and steroids to provide excellent graft survival in the
absence of calcineurin inhibitors. Steroid side-effects can be lessened by tapering the
steroid dose to an every-other-day schedule. This protocol tests whether immunosuppression
by IL-2r antibody, sirolimus, MMF, and alternate-day steroids will provide comparable graft
survival for living donor recipients, compared to current immunosuppression, but with
reduced complications of calcineurin inhibitors.
Evaluations prior to transplantation include a complete history and physical examination,
CBC, liver function tests, and antibodies for CMV, EBV, HIV, HbsAG, and HCV. All appropriate
vaccinations are provided before transplantation. Transplant recipients receive
immunosuppression therapy using antibody induction (daclizumab), corticosteroids,
mycophenolate mofetil, and sirolimus. Serum sirolimus levels are measured so that doses can
be adjusted to maintain certain blood levels of the drug. Bactrim and ganciclovir are given
for infection prophylaxis. If the patient has consistent high levels of fasting cholesterol,
treatment with lipitor may be given. A transplant biopsy is performed at the time of the
transplant and at 3, 6, and 12 months post transplantation and at times when a rejection is
suspected. A radionuclide GFR is done at the same time points, and at 1, 24, and 36 months.
The protocol biopsies, blood, and urine samples will be analyzed by genomic methods to
determine differences in gene expression post transplantation. In the event of a first acute
rejection, patients are treated with Solu-Medrol for 3 consecutive days. A second rejection
(at the discretion of the transplant center) or severe rejection (Banff Grade 3) is treated
with antibody therapy and, after a second or severe rejection, the immunosuppressant regimen
is changed. Patients are followed for 36 months with routine physical examinations and
Patients may be eligible for this study if they:
- Are 21 years of age and under.
- Are kidney recipients of living-donor grafts, except when living-donor grafts are
Patients will not be eligible for this study if they:
- Are recipients of identical (HLA matched) living-donor grafts.
- Are recipients of cadaver-donor grafts.
- Have certain abnormal kidney diseases that may return.
- Have failed 2 or more previous kidney transplants.
- Have fat abnormalities that are inherited or present at high levels.