The objective of this study is to compare the effects of two liver transplant
immunosuppression regimens on renal function. Patients receiving the standard combination of
prednisone and high-dose tacrolimus, a drug with known nephrotoxicity (Arm A) will be
compared to patients receiving prednisone, low-dose tacrolimus and mycophenolate mofetil
(MMF) (Arm B). MMF is an immunosuppression agent that has no associated nephrotoxicity. The
primary end point of the study will be renal function as measured by glomerular filtration
rate (GFR). Thirty pediatric liver transplant recipients will be randomized to these two
arms in a 1:1 ratio (i.e. 15 patients in each group). Secondary end points will measure
patient and graft outcome and incidence of immunosuppression-related complications,
including: neurotoxicity, diabetes mellitus, growth retardation, vomiting, diarrhea,
gastrointestinal hemorrhage, thrombocytopenia, anemia, leukopenia, acute or chronic liver
graft rejection, posttransplant lymphoproliferative disease (PTLD), viral infections, fungal
infections and bacterial infections.
- End-stage liver disease or acute fulminant hepatic failure recalcitrant to
conventional medical or surgical therapy.
- Listed as candidate for pediatric liver transplantation listed with United Network
for Organ Sharing (UNOS).
- Patients must be 18 years of age or younger.
- History of autoimmune disease or primary sclerosing cholangitis.
- History of end-stage renal disease, dialysis treatment or acute renal failure (not
including hepatorenal syndrome).
- Patients with pretransplant renal insufficiency as determined by a glomerular
filtration rate (GFR) of <80 mL/min/1.73m2 (see below).
- Patients with renal agenesis or hypoplasia, polycystic kidney disease, or hydroureter
seen on pretransplant renal ultrasound.
- Patients with malignancy or previous malignancy.
- Patients with active bacterial, viral, or fungal infections.
- Patients with a pretransplant diagnosis of diabetes mellitus.
- Patients with history of previous transplant or multi-organ recipients.
- Patients with serological evidence of HIV, HBSAg or HCV.
- Patients with hereditary syndrome that causes genetic deficiency of
hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan or
- Patients with history of phenylketonuria.
- Females that are pregnant or breastfeeding.
- Sexually active females who are not: a) post-menopausal, or b) surgically sterile,
and c) using an acceptable method of contraception (oral contraceptive, implanted
devices, injection, and barrier devices are acceptable; condoms used alone are not
- Patients with alcohol abuse, substance abuse or smoking within the previous 6 months.
- Patients or caretakers of patients with psychogenic factors that preclude therapeutic
- Inability to reach participating hospital within 2 hours of notification.
- Any conditions or any circumstance that makes it unsafe to undergo a liver