Mycophenolate mofetil and reduced doses of cyclosporine in pediatric liver transplantation with chronic renal dysfunction: changes in the immune responses.
The aim of this study was to study the incidence of chronic renal dysfunction in patients with more than 5 yr of follow-up following liver transplantation and to evaluate the benefit of decreasing cyclosporine A (CsA) dose combined with mycophenolate mofetil (MMF) on renal function and immune response in these patients. Between 1988 and 1994, 60 children were transplanted, and 86% survived >5 yr post-liver transplantation. Fourteen patients developed chronic renal dysfunction secondary to CsA toxicity as evaluated by renal biopsy. In 11 patients CsA dose was decreased to 40-90 mg/ml target levels and MMF 600 mg/m(2) twice daily was added to the immunosuppressive regimen. Plasma creatinine decreased (from 1.0 +/- 0.03 to 0.8 +/- 0.03 ng/dl, p < 0.007), creatinine clearance increased (from 66.8 +/- 3.0 to 99.2 +/- 6.3 ml/min/1.73 m(2), p < 0.002) and microalbuminuria decreased (from 21.0 +/- 8.6 to 3.6 +/- 1.1 mg/24 h, p < 0.05) after 12 months of CsA combined with MMF therapy. During combined therapy the proliferative, cytolytic response and cytotoxic antibodies showed no significant changes, whereas CD4/CD8 ratio increased (from 1.2 +/- 0.2 to 1.4 +/- 0.1, p < 0.05). Tumor necrosis factor-alpha secretion increased (p < 0.005) during MMF therapy. The release of interleukin-10 was strikingly augmented under both immunosuppressive regimens, but the release of transforming growth factor-beta and interferon-gamma did not change. Our findings indicate that initiation of MMF combined with reduced doses of CsA allowed the recovery of renal function with minor changes in the immune response.
Ferraris
Jorge R
JR
Servicio de Nefrología Pediátrica, Hospital Italiano, Buenos Aires, Argentina. jferraris@intramed.net.ar
Duca
Pablo
P
Prigoshin
Norma
N
Tambutti
Monica L
ML
Boldrini
Gustavo
G
Cardoni
Rita L
RL
D'Agostino
Daniel
D
D000293:Adolescent; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D016031:Liver Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D016572:Cyclosporine; D009173:Mycophenolic Acid