Abstract
Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy.
| Original language | English |
|---|---|
| Pages (from-to) | 379-387 |
| Number of pages | 9 |
| Journal | American Journal of Transplantation |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2012 |
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Keywords
- Allograft loss
- kidney transplantation
- mortality
- mTOR inhibitors
ASJC Scopus subject areas
- Transplantation
- Immunology and Allergy
- Pharmacology (medical)
Cite this
Clinical outcomes in kidney transplant recipients receiving long-term therapy with inhibitors of the mammalian target of rapamycin. / Cortazar, F.; Molnar, M. Z.; Isakova, T.; Czira, M. E.; Kovesdy, C. P.; Roth, David; Mucsi, I.; Wolf, M.
In: American Journal of Transplantation, Vol. 12, No. 2, 01.02.2012, p. 379-387.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical outcomes in kidney transplant recipients receiving long-term therapy with inhibitors of the mammalian target of rapamycin
AU - Cortazar, F.
AU - Molnar, M. Z.
AU - Isakova, T.
AU - Czira, M. E.
AU - Kovesdy, C. P.
AU - Roth, David
AU - Mucsi, I.
AU - Wolf, M.
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy.
AB - Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy.
KW - Allograft loss
KW - kidney transplantation
KW - mortality
KW - mTOR inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84856427202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856427202&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2011.03826.x
DO - 10.1111/j.1600-6143.2011.03826.x
M3 - Article
C2 - 22054244
AN - SCOPUS:84856427202
VL - 12
SP - 379
EP - 387
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 2
ER -