Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation.
BACKGROUND
Cyclosporine A (CsA) and tacrolimus (Tac) provide effective immunosuppression after orthotopic liver transplantation (OLT) but can cause renal dysfunction that may progress to end-stage renal failure (ESRF). Mycophenolate mofetil (MMF) is a newer immunosuppressant that does not affect renal function. Its long-term use in children with renal dysfunction after OLT has not yet been fully evaluated.


METHODS
A retrospective analysis was performed of all children begun on MMF for renal dysfunction and followed up for at least 1 year. Renal dysfunction was defined as calculated glomerular filtration rate (cGFR) of less than 65 mL/min/1.73 m2. cGFR and liver function were measured before and after transfer. Data were analyzed using the Wilcoxon signed rank test.


RESULTS
Forty-eight children (23 males) began MMF at a median age of 11.1 (0.9-18.1) years and at a median of 4.0 (0.3-12.4) years postOLT. Median baseline cGFR was 54 (range 29-65) mL/min/1.73 m2. Immunosuppression after transfer was MMF monotherapy in 36, MMF with steroids, in 4 and MMF with low-dose CsA or Tac in 8. In 44 (92%) patients, there was a statistically significant increase to a median cGFR of 69 (28-114) mL/min/1.73 m2 by 1 month and a further increase to a median cGFR of 77 (24-105) mL/min/1.73 m2 by 2 months of MMF treatment, after which time cGFR was maintained. Children aged less than 3 years at OLT or who were less than 5 years postOLT when MMF was begun demonstrated greater increases in cGFR. Four children with a median baseline cGFR of 34 (range 31-49) mL/min/1.73 m2 did not respond and progressed to ESRF. Mild side effects occurred in seven (15%) and gastrointestinal bleeding requiring discontinuation of MMF in one (2%). Liver function abnormalities occurred in seven (15%): transient transaminitis in three, acute rejection in two, and chronic rejection in two, of whom one required retransplantation.


CONCLUSIONS
In 92% children with renal dysfunction after OLT, MMF treatment provided safe and effective immunosuppression and allowed CsA or Tac to be discontinued or reduced, leading to improvement of renal function. The improvement was greatest in younger children and those who began MMF early postOLT. Side effects were uncommon. Additional steroid cover during the transfer to MMF should be considered to prevent liver-allograft rejection.
Evans
Helen M
HM
The Liver Unit, Birmingham Children's Hospital, Birmingham B4 6NH, UK. helenevans@doctors.org.uk
McKiernan
Patrick J
PJ
Kelly
Deirdre A
DA
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002857:Chromium / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008107:Liver Diseases / Q000453:epidemiology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008657:Metabolic Clearance Rate; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000145:classification* / Q000453:epidemiology; D012189:Retrospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D002857:Chromium; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid