Conversion from cyclosporine A to tacrolimus in pediatric kidney transplant recipients with chronic rejection: Changes in the immune responses

Background. Tacrolimus (Tac) has immunosuppressant properties similar to those of cyclosporine A (CsA), but it is more potent. At present, however, its immunosuppressive activity in renal transplant recipients with ongoing chronic rejection has not been clarified. Methods. We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, cytotoxic antibodies, lymphocyte population, and cytokine response before and after the conversion from CsA to Tac in 14 pediatric renal transplant recipients with chronic rejection. CsA (5.9 +/- 0.2 mg/kg/d) was replaced by Tac (0.1 +/- 0.004 mg/kg/d). Results. Serum creatinine decreased (2.3 +/- 0.2 - 1.9 +/- 0.2 mg/dL, P < 0.005), creatinine clearance increased (36.8 +/- 2.5 - 46.1 +/- 4.4 mL/min/1.73m(2), P < 0.005), and urinary protein excretion decreased (0.4 +/- 0.01 - 0.2 +/- 0.04 g/24 hr, P < 0.03) after 6 months, and these values were maintained after 2 years with Tac treatment. During Tac therapy, anti-donor and anti-control mixed lymphocyte culture decreased 38% and 31% (P < 0.05), respectively. Cell-mediated lympholysis did not change. CD3(+) decreased from 87% +/- 2% to 80% +/- 2% (P < 0.005), and CD8(+) decreased from 34 +/- 3% to 27% +/- 2% (P < 0.005). The switch to Tac decreased the interferon-gamma production in vitro (P < 0.05) and increased tumor necrosis factor-alpha levels (P < 0.05). The release of interleukin-10 was strikingly augmented with CsA or Tac therapy (P < 0.01), but transforming growth factor-beta secretion was similar. Conclusions. Our data indicate that conversion from CsA to Tac therapy leads to an improvement in renal function without altering key elements of the immunosuppression in children with ongoing chronic rejection.