TY - JOUR
T1 - Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients
T2 - 24-month efficacy and safety results from the CONVERT trial
AU - Schena, Francesco P.
AU - Pascoe, Michael D.
AU - Alberu, Josefina
AU - Del Carmen Rial, Maria
AU - Oberbauer, Rainer
AU - Brennan, Daniel C.
AU - Campistol, Josep M.
AU - Racusen, Lorraine
AU - Polinsky, Martin S.
AU - Goldberg-Alberts, Robert
AU - Li, Huihua
AU - Scarola, Joseph
AU - Neylan, John F.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2009/1/27
Y1 - 2009/1/27
N2 - BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.
AB - BACKGROUND.: The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated. METHODS.: Eight hundred thirty renal allograft recipients, 6 to 120 months posttransplant and receiving cyclosporine or tacrolimus, were randomly assigned to continue CNI (n=275) or convert from CNI to SRL (n=555). Primary endpoints were calculated Nankivell glomerular filtration rate (GFR; stratified at baseline: 20-40 vs. >40 mL/min) and the cumulative rates of biopsy-confirmed acute rejection (BCAR), graft loss, or death at 12 months. Enrollment in the 20 to 40 mL/min stratum was halted prematurely because of a higher incidence of safety endpoints in the SRL conversion arm. RESULTS.: Intent-to-treat analyses at 12 and 24 months showed no significant treatment difference in GFR in the baseline GFR more than 40 mL/min stratum. On-therapy analysis of this cohort showed significantly higher GFR at 12 and 24 months after SRL conversion. Rates of BCAR, graft survival, and patient survival were similar between groups. Median urinary protein-to-creatinine ratios (UPr/Cr) were similar at baseline but increased significantly after SRL conversion. Malignancy rates were significantly lower at 12 and 24 months after SRL conversion. Post hoc analyses identified a subgroup with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11, whose risk-benefit profile was more favorable after conversion than that for the overall SRL conversion cohort. CONCLUSIONS.: At 2 years, SRL conversion among patients with baseline GFR more than 40 mL/min was associated with excellent patient and graft survival, no difference in BCAR, increased urinary protein excretion, and a lower incidence of malignancy compared with CNI continuation. Superior renal function was observed among patients who remained on SRL through 12 to 24 months, particularly in the subgroup of patients with baseline GFR more than 40 mL/min and UPr/Cr less than or equal to 0.11.
KW - Calcineurin inhibitor
KW - Immunosuppression
KW - Kidney transplantation
KW - Sirolimus
UR - http://www.scopus.com/inward/record.url?scp=59649126728&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649126728&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3181927a41
DO - 10.1097/TP.0b013e3181927a41
M3 - Article
C2 - 19155978
AN - SCOPUS:59649126728
SN - 0041-1337
VL - 87
SP - 233
EP - 242
JO - Transplantation
JF - Transplantation
IS - 2
ER -