Cyclosporine in pediatric kidney transplantation

Abstract

Before the era of cyclosporine (CsA), immunosuppression with azathioprine and steroids resulted in high rejection rates and severe growth retardation in pediatric renal transplant recipients. In the early 1980s, immunosuppression with CsA was introduced for children. Because of differences in metabolism rates and relation of weight and body surface area, special pediatric dosing regimens and monitoring strategies had to be developed. Use of CsA led to a decreased number of acute rejections and, consequently, to a marked increase in graft survival rates. The growth rates of transplanted children were significantly higher under CsA-based immunosuppression than with classical regimens. This was due to a decreased need of steroid co-administration. Main side effects of CsA in children were nephrotoxicity and hirsutism. The introduction of CsA microemulsion in the 1990s led to more reliable absorption profiles and to a lower interindividual variability of CsA area-under-the-curve concentrations and thus to another improvement in rejection rates. New monitoring strategies, based on CsA levels taken 2 hours' postdose, seem promising. In pediatric transplantation, CsA is often successfully combined with an antibody-induction therapy in order to reduce the number of early acute rejections. Combination with mycophenolate mofetil reduces the appearance of chronic rejection. Additional therapy with ToR inhibitors might enforce a reduction of CsA doses and therefore lead to a reduction of CsA toxic effects.