TY - JOUR
T1 - Minimization of Maintenance Immunosuppression Early After Renal Transplantation: An Interim Analysis
AU - Bemelman, Frederike J.
AU - de Maar, Eltjo F.
AU - Press, Rogier R.
AU - van Kan, Henrikus J.
AU - ten Berge, Ineke J.
AU - Homan van der Heide, Jaap J.
AU - de Fijter, Hans W.
PY - 2009
Y1 - 2009
N2 - Introduction. Chronic allograft nephropathy is the main cause of long-term renal transplant failure. Chronic use of calcineurin inhibitors contributes to its pathogenesis. Here, we report on a multicenter randomized trial to study the effects of withdrawal of cyclosporine A (CsA) from a triple immunosuppressive regimen containing CsA, prednisolone (P), and mycophenolate sodium (MPS) early after transplantation. Methods. Patients continued on P/CsA, P/MPS, or P and everolimus (EVL). Before withdrawal, a transplant biopsy was performed ensuring no subclinical rejection was present. Drug levels were closely monitored. The primary outcome was interstitial graft fibrosis and hyalinosis. Secondary outcome was among others graft rejection. Results. According to trial regulations, an interim analysis was performed after enrollment of half of the intended number of patients (n = 113). Mean follow-up was 14 5 months from transplantation and 8 +/- 5 months from conversion. After conversion, acute rejection percentages were 3% in the P/CsA group, 22% in the P/MPS group, and 0% in the P/EVL group (P <0.009). Conclusions. We conclude that switching immunosuppressive therapy from P/CsA/MPS to therapy with P/CsA or P/EVL at 6 months after renal transplantation is effective in preventing rejection. Double therapy with P/MPS after withdrawal of P/CsA resulted in an increase in severe acute rejection episodes. These results were the immediate reason to halt the P/MPS arm. Serum creatinine values at the latest follow-up (8 +/- 5 months after conversion and 14 +/- 5 months after transplantation) in the P/EVL group were lower than in the P/CsA group
AB - Introduction. Chronic allograft nephropathy is the main cause of long-term renal transplant failure. Chronic use of calcineurin inhibitors contributes to its pathogenesis. Here, we report on a multicenter randomized trial to study the effects of withdrawal of cyclosporine A (CsA) from a triple immunosuppressive regimen containing CsA, prednisolone (P), and mycophenolate sodium (MPS) early after transplantation. Methods. Patients continued on P/CsA, P/MPS, or P and everolimus (EVL). Before withdrawal, a transplant biopsy was performed ensuring no subclinical rejection was present. Drug levels were closely monitored. The primary outcome was interstitial graft fibrosis and hyalinosis. Secondary outcome was among others graft rejection. Results. According to trial regulations, an interim analysis was performed after enrollment of half of the intended number of patients (n = 113). Mean follow-up was 14 5 months from transplantation and 8 +/- 5 months from conversion. After conversion, acute rejection percentages were 3% in the P/CsA group, 22% in the P/MPS group, and 0% in the P/EVL group (P <0.009). Conclusions. We conclude that switching immunosuppressive therapy from P/CsA/MPS to therapy with P/CsA or P/EVL at 6 months after renal transplantation is effective in preventing rejection. Double therapy with P/MPS after withdrawal of P/CsA resulted in an increase in severe acute rejection episodes. These results were the immediate reason to halt the P/MPS arm. Serum creatinine values at the latest follow-up (8 +/- 5 months after conversion and 14 +/- 5 months after transplantation) in the P/EVL group were lower than in the P/CsA group
U2 - https://doi.org/10.1097/TP.0b013e3181af1df6
DO - https://doi.org/10.1097/TP.0b013e3181af1df6
M3 - Article
C2 - 19667948
SN - 0041-1337
VL - 88
SP - 421
EP - 428
JO - Transplantation
JF - Transplantation
IS - 3
ER -