Mycophenolate mofetil and reduced doses of cyclosporine in pediatric liver transplantation with chronic renal dysfunction: Changes in the immune responses

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-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.

Adverse Effects of Immunosuppression in Pediatric Solid Organ Transplantation

“…Following the addition of mycophenolate mofetil in children experiencing CAN following kidney transplantation, renal function improved in as many as 61% of patients, without a reduction in ciclosporin or tacrolimus dose. [101] Several studies have confirmed the benefits of adding mycophenolate mofetil after reducing the dose of ciclosporin or tacrolimus in pediatric liver [102] and heart transplant recipients. [103] Sirolimus has also been used as a rescue agent for nephrotoxicity associated with ciclosporin and tacrolimus.…”

Indications of Mycophenolate Mofetil in Liver Transplantation

“…Mean creatinine clearance increased significantly from 44.7 ml/min to 55.1 ml/min within 18 months (Pϭ0.0001). Ferraris et al (44) showed that MMF treatment in pediatric liver transplant recipients could reach comparable results to improve chronic renal dysfunction: 14 out of 60 transplanted children developed renal dysfunction. After start of MMF treatment renal function improved significantly with serum creatinine levels lowering from 1.0Ϯ0.03 mg/dL to 0.8Ϯ0.03 mg/dL (PϽ0.007) and an increasing creatinine clearance from 66.8Ϯ3.0 ml/min to 99.2Ϯ6.3 ml/min (PϽ0.002) within 12 months.…”

The adolescent and liver transplantation

“…If these patients were taking cyclosporine or tacrolimus as their main immunosuppressant, mycophenolate mofetil enabled a reduction in the dose of calcineurin inhibitors (CNI), and even their complete withdrawal in some cases, with a concomitant improvement in renal function [12][13][14][15][16][17]. A beneficial effect was also shown in the 62% of patients whose liver dysfunction was due to acute cellular rejection (Table 1).…”