What is the calcineurin inhibitor of choice for pediatric renal transplantation?
Cyclosporine microemulsion (CyA) and tacrolimus (Tac) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. In the majority of patients, these calcineurin inhibitors have been used in combination with other immunosuppressive drugs, such as azathioprine or mycophenolate mofetil (MMF). In this review we will address the question of what calcineurin inhibitor we should use in an individual pediatric renal transplant patient. Well-designed randomized studies in children showed no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However Tac is significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population when used in conjunction with azathioprine and corticosteroids. This difference disappears when calcineurin inhibitors are used in combination with MMF as both Tac and CyA produce similar rejection rates and graft survival. However, Tac is associated with improved graft function at 1 and 2 yr post-transplant. Adverse events of hypomagnesaemia and diarrhea seem to be higher in Tac group whereas hypertrichosis, flu syndrome and gum hyperplasia occurs more frequently in the CyA group. The incidence of post-transplant diabetes mellitus was almost identical between Tac and CyA treated patients. The recommendation drawn from the available data is that both CyA and Tac can be used safely and effectively in children. However Tac may be preferable to CyA because of steroid sparing effect and less hirsutism. We recommend that cyclosporine should be chosen when patients experience Tac-related adverse events. Nevertheless, the best calcineurin inhibitor should be decided on individual patients according to variable risk factors, such as risk of rejection in sensitized patient or delayed graft function. The possibility of adverse events should also be considered.
Kari
Jameela A
JA
Pediatrics Department, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia.
Trompeter
Richard S
RS
D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002648:Child; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D048788:Growth and Development / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000139:chemically induced; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011182:Postoperative Care; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus; D016559:Tacrolimus