Pediatric Kidney Transplant Study of Sirolimus, Mycophenolate Mofetil, and Corticosteroids vs Calcineurin Inhibitor Based Immunosuppression (CNI-W)

• This study has a primary endpoint of allograft function as determined by Schwartz GFR at 18 months after conversion to CNI free protocol (2 years post transplantation). [ Time Frame: 18 mos after conversion to CNI free protocol ] [ Designated as safety issue: Yes ]
  

• Secondary outcomes will include biopsy proven acute rejection episodes, progression of quantitative interstitial fibrosis as determined by Sirius Red staining and digital image analysis, Allograft survival and patient survival [ Time Frame: measured at 12 and 24 months post transplant ] [ Designated as safety issue: Yes ]
  

Advances in immunosuppressive therapies in pediatrics have been associated with rapidly falling incidence of acute rejection and improving allograft survival. In recent analyses of the NAPRTCS database, acute rejection is no longer the most common cause of hospitalization or allograft failure. Chronic rejection has now become the most common cause of allograft failure and accounts for over 35% of allograft loss. Chronic rejection is a complex clinical condition that includes both immunologic and non-immunologic causes and is more accurately referred to as Chronic Allograft Nephropathy (CAN). Although Calcineurin inhibitors (CNI) have played a central role in reducing acute rejection and improving allograft survival, it has long been shown that they contribute to interstitial fibrosis and chronic allograft nephropathy. Recent trials in adult transplantation have demonstrated that with the use of the TOR-inhibitor, Sirolimus, it is possible to withdraw Calcineurin inhibitors with no increase in rejection and with improvements in allograft function, interstitial fibrosis and long term survival (1). We hypothesize that the use of Sirolimus (SRL) in pediatric kidney transplantation will allow the withdrawal of Calcineurin inhibitor and improved kidney function and long term survival. We plan to enroll 50 patients at the time of transplantation. Patients will receive routine immunosuppression of CNI (Prograf), Mycophenolate mofetil (Cellcept) and prednisone. Those patients with normal function and no rejection episodes after 6 months of transplantation will undergo a slow conversion from Prograf to Sirolimus (Rapamune). We will then assess the rate of rejection, allograft function, fibrosis on biopsy, and allograft survival over the following 18 months.