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Mycophenolate mofetil and reduced doses of cyclosporine in pediatric liver transplantation with chronic renal dysfunction: Changes in the immune responses
Author(s) -
Ferraris Jorge R.,
Duca Pablo,
Prigoshin Norma,
Tambutti Monica L.,
Boldrini Gustavo,
Cardoni Rita L.,
D'Agostino Daniel
Publication year - 2004
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2004.00172.x
Subject(s) - medicine , transplantation , renal function , gastroenterology , mycophenolic acid , creatinine , urology , mycophenolate , regimen
Abstract: 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‐ α 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‐ β and interferon‐ γ 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.