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Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study

Frei, Ulrich; Daloze, Pierre; Vitko, Stefan; Klempnauer, Juergen; Reyes-Acevedo, Rafael; Titiz, Izzet; Fricke, Lutz; Bernasconi, Corrado and Ekberg, Henrik LU (2010) In Clinical Transplantation 24(4). p.500-509
Abstract
The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (>= grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months.... (More)
The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (>= grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mycophenolate mofetil, acute rejection, cyclosporine, sirolimus, tacrolimus
in
Clinical Transplantation
volume
24
issue
4
pages
500 - 509
publisher
Wiley-Blackwell
external identifiers
  • wos:000280991700016
  • scopus:77955755249
ISSN
1399-0012
DOI
10.1111/j.1399-0012.2009.01093.x
language
English
LU publication?
yes
id
e4cff19f-84ea-436a-b0a1-28bd1df021df (old id 1673935)
date added to LUP
2010-09-22 15:39:30
date last changed
2018-05-29 10:42:05
@article{e4cff19f-84ea-436a-b0a1-28bd1df021df,
  abstract     = {The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (>= grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.},
  author       = {Frei, Ulrich and Daloze, Pierre and Vitko, Stefan and Klempnauer, Juergen and Reyes-Acevedo, Rafael and Titiz, Izzet and Fricke, Lutz and Bernasconi, Corrado and Ekberg, Henrik},
  issn         = {1399-0012},
  keyword      = {mycophenolate mofetil,acute rejection,cyclosporine,sirolimus,tacrolimus},
  language     = {eng},
  number       = {4},
  pages        = {500--509},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Transplantation},
  title        = {Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study},
  url          = {http://dx.doi.org/10.1111/j.1399-0012.2009.01093.x},
  volume       = {24},
  year         = {2010},
}