Role of mizoribine in renal transplantation.

Renal transplantation is the optimal form of therapy for children and adolescents with end-stage renal disease. Usually histocompatibility differences exist between donor and recipient, so it is necessary to modify or suppress the immune response to enable the recipient to accept a graft. Calcineurin inhibitors (CNI), which include cyclosporin (CsA) and tacrolimus (FK506), give many benefits on the outcome after renal transplantation, but have some toxic effects, especially nephrotoxicity. Therefore, inhibitors of purine synthesis revived as newer generation of more specific inhibitors, mizoribine (MZ) and mycophenolate mofetil (MMF). The Japanese pediatric renal transplantation clinical study group attempted to reduce and then discontinue steroid administration in combination with another three immunosuppressive drugs, CsA, MZ and anti-lymphocyte globulin (ALG). This study showed good clinical results. Mizoribine is an effective immunosuppressive drug in human renal transplantation. However, it is not as popular as other inhibitors of purine synthesis, such as azathioprine (AZA) and MMF, because MZ has been used mainly in Japan and infrequently in other countries. However, MZ is a more useful immunosuppressive drug than AZA, when it is used in combination with CNI.