TY - JOUR
T1 - Inhibitors of mTOR and risks of allograft failure and mortality in kidney transplantation
AU - Isakova, T.
AU - Xie, H.
AU - Messinger, S.
AU - Cortazar, F.
AU - Scialla, J. J.
AU - Guerra, G.
AU - Contreras, G.
AU - Roth, D.
AU - Burke, G. W.
AU - Molnar, M. Z.
AU - Mucsi, I.
AU - Wolf, M.
PY - 2013/1
Y1 - 2013/1
N2 - Data on long-term outcomes of users of inhibitors of the mammalian target of rapamycin (mTORI) are lacking in kidney transplantation. In an analysis of 139 370 US kidney transplant recipients between 1999 through 2010, we compared clinical outcomes among users of mTORIs versus calcineurin inhibitors (CNI) in their primary immunosuppresive regimen. During the first 2 years posttransplantation, primary use of mTORIs without CNIs (N = 3237) was associated with greater risks of allograft failure and death compared with a CNI-based regimen (N = 125 623); the hazard ratio (HR) of the composite outcome ranged from 3.67 (95% confidence interval [CI], 3.12-4.32) after discharge to 1.40 (95% CI 1.26-1.57) by year 2. During years 2-8, primary use of mTORIs without CNIs was independently associated with greater risks of death (HR 1.25; 95% CI, 1.11-1.41) and the composite (HR 1.17; 95%CI, 1.08-1.27) in fully adjusted analyses. The results were qualitatively unchanged in subgroups defined by medical history, immunological risk and clinical course during the index transplant hospitalization. In a propensity-score matched cohort, use of mTORIs was associated with significantly worse outcomes during the first 2 years and greater risks of death (HR 1.21; 95% CI, 1.05-1.39) and the composite (HR 1.18; 95% CI, 1.08-1.30) in years 2-8. Compared with CNI-based regimens, use of an mTORI-based regimen for primary immunosuppression in kidney transplantation was associated with inferior recipient survival. The authors conduct an observational study of 139,370 recipients who underwent kidney transplantation between 1999 and 2010 in the United States and find that compared with calcineurin-inhibitor-based regimens, use of mammalian target of rapamycin-based regimens for primary immunosuppression is associated with inferior recipient survivals.
AB - Data on long-term outcomes of users of inhibitors of the mammalian target of rapamycin (mTORI) are lacking in kidney transplantation. In an analysis of 139 370 US kidney transplant recipients between 1999 through 2010, we compared clinical outcomes among users of mTORIs versus calcineurin inhibitors (CNI) in their primary immunosuppresive regimen. During the first 2 years posttransplantation, primary use of mTORIs without CNIs (N = 3237) was associated with greater risks of allograft failure and death compared with a CNI-based regimen (N = 125 623); the hazard ratio (HR) of the composite outcome ranged from 3.67 (95% confidence interval [CI], 3.12-4.32) after discharge to 1.40 (95% CI 1.26-1.57) by year 2. During years 2-8, primary use of mTORIs without CNIs was independently associated with greater risks of death (HR 1.25; 95% CI, 1.11-1.41) and the composite (HR 1.17; 95%CI, 1.08-1.27) in fully adjusted analyses. The results were qualitatively unchanged in subgroups defined by medical history, immunological risk and clinical course during the index transplant hospitalization. In a propensity-score matched cohort, use of mTORIs was associated with significantly worse outcomes during the first 2 years and greater risks of death (HR 1.21; 95% CI, 1.05-1.39) and the composite (HR 1.18; 95% CI, 1.08-1.30) in years 2-8. Compared with CNI-based regimens, use of an mTORI-based regimen for primary immunosuppression in kidney transplantation was associated with inferior recipient survival. The authors conduct an observational study of 139,370 recipients who underwent kidney transplantation between 1999 and 2010 in the United States and find that compared with calcineurin-inhibitor-based regimens, use of mammalian target of rapamycin-based regimens for primary immunosuppression is associated with inferior recipient survivals.
KW - Allograft failure
KW - kidney transplantation
KW - mTOR inhibitors
KW - mortality
UR - http://www.scopus.com/inward/record.url?scp=84871717946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871717946&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2012.04281.x
DO - 10.1111/j.1600-6143.2012.04281.x
M3 - Article
C2 - 23025566
AN - SCOPUS:84871717946
SN - 1600-6135
VL - 13
SP - 100
EP - 110
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 1
ER -