TY - JOUR
T1 - Improved renal function after early conversion from a calcineurin inhibitor to everolimus
T2 - a randomized trial in kidney transplantation
AU - Mjörnstedt, L
AU - Sørensen, S S
AU - von Zur Mühlen, B
AU - Jespersen, B
AU - Hansen, J M
AU - Bistrup, Christian Henning
AU - Andersson, H
AU - Gustafsson, B
AU - Undset, L H
AU - Fagertun, H
AU - Solbu, D
AU - Holdaas, H
N1 - © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2012/10
Y1 - 2012/10
N2 - In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent. In a randomized, open-label, multicenter study, conversion from cyclosporine to everolimus at week 7 after kidney transplantation improves one-year renal function, but is also associated with a higher rate of rejections and withdrawals due to adverse events.
AB - In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent. In a randomized, open-label, multicenter study, conversion from cyclosporine to everolimus at week 7 after kidney transplantation improves one-year renal function, but is also associated with a higher rate of rejections and withdrawals due to adverse events.
U2 - 10.1111/j.1600-6143.2012.04162.x
DO - 10.1111/j.1600-6143.2012.04162.x
M3 - Journal article
C2 - 22812414
SN - 1600-6135
VL - 12
SP - 2744
EP - 2753
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 10
ER -