TY - JOUR
T1 - Randomized trial of 3 maintenance regimens (TAC/SRL vs. TAC/MMF vs. CSA/SRL) with low-dose corticosteroids in primary kidney transplantation
T2 - 18-year results
AU - Ciancio, Gaetano
AU - Gaynor, Jeffrey J.
AU - Guerra, Giselle
AU - Roth, David
AU - Chen, Linda
AU - Kupin, Warren
AU - Mattiazzi, Adela
AU - Ortigosa-Goggins, Mariella
AU - Moni, Lissett
AU - Burke, George W.
N1 - Funding Information:
There were no funding sources to declare for the performance of this study.
PY - 2020/12
Y1 - 2020/12
N2 - A randomized trial of 150 primary kidney transplant recipients, initiated in May 2000, compared tacrolimus (TAC)/sirolimus (SRL) vs. TAC/mycophenolate mofetil (MMF) vs. cyclosporine microemulsion (CSA)/SRL (N = 50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow-up of 18 years post-transplant, biopsy-proven acute rejection (BPAR) occurred less often in TAC/MMF (26% (13/50)), vs. the TAC/SRL (36% (18/50)) and CSA/SRL (34% (17/50)) arms combined (p =.23), with statistical significance favoring TAC/MMF (p =.05) after controlling for the multivariable (Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0–1 (N = 72) vs. 2–3 (N = 78) unfavorable baseline characteristics (recipient age <50 years, African American or Hispanic recipient, and donor age ≥50 years) (p =.02). Mean estimated glomerular filtration rate (eGFR), using the CKD-EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96 months post-transplant (p ≤.008). These differences were translated into an observed more favorable graft failure due to immunologic cause (CAI/TG) rate for TAC/MMF (p =.06), although no significant differences in overall death-uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement for antilipid therapy rates in the SRL-assigned arms were maintained over time. Overall, these results at 18 years post-transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long-term maintenance immunosuppression in kidney transplantation.
AB - A randomized trial of 150 primary kidney transplant recipients, initiated in May 2000, compared tacrolimus (TAC)/sirolimus (SRL) vs. TAC/mycophenolate mofetil (MMF) vs. cyclosporine microemulsion (CSA)/SRL (N = 50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow-up of 18 years post-transplant, biopsy-proven acute rejection (BPAR) occurred less often in TAC/MMF (26% (13/50)), vs. the TAC/SRL (36% (18/50)) and CSA/SRL (34% (17/50)) arms combined (p =.23), with statistical significance favoring TAC/MMF (p =.05) after controlling for the multivariable (Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0–1 (N = 72) vs. 2–3 (N = 78) unfavorable baseline characteristics (recipient age <50 years, African American or Hispanic recipient, and donor age ≥50 years) (p =.02). Mean estimated glomerular filtration rate (eGFR), using the CKD-EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96 months post-transplant (p ≤.008). These differences were translated into an observed more favorable graft failure due to immunologic cause (CAI/TG) rate for TAC/MMF (p =.06), although no significant differences in overall death-uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement for antilipid therapy rates in the SRL-assigned arms were maintained over time. Overall, these results at 18 years post-transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long-term maintenance immunosuppression in kidney transplantation.
KW - biopsy-proven acute rejection
KW - cause-specific graft loss
KW - cyclosporine microemulsion
KW - estimated glomerular filtration rate
KW - kidney transplantation
KW - mycophenolate mofetil
KW - sirolimus
KW - tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=85096653749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096653749&partnerID=8YFLogxK
U2 - 10.1111/ctr.14123
DO - 10.1111/ctr.14123
M3 - Article
C2 - 33070366
AN - SCOPUS:85096653749
VL - 34
JO - Clinical Transplantation
JF - Clinical Transplantation
SN - 0902-0063
IS - 12
M1 - e14123
ER -