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Minimization of immunosuppressive therapy after renal transplantation: Results of a randomized controlled trial

Vanrenterghem, Y; van Hooff, JP; Squifflet, JP; Salmela, K; Rigotti, P; Jindal, RM; Pascual, J; Ekberg, Henrik LU ; Sicilia, LS and Boletis, JN, et al. (2005) In American Journal of Transplantation 5(1). p.87-95
Abstract
Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and... (More)
Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications. The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol (18.9 mg/dL [0.49 mmol/L]) and LDL-cholesterol (8.1 mg/dL [0.21 mmol/L]) between months 4 and 6 were greater in the steroid stop group (p < 0.001). Leukopenia (p = 0.0082), serious CMV infection (p = 0.024), anemia (p = NS) and diarrhea (p = NS) were less frequent in the MMF stop group. In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy. (Less)
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publishing date
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Contribution to journal
publication status
published
subject
keywords
tacrolimus, MMF withdrawal, minimization of immunosuppression, transplantation, kidney, corticosteroid withdrawal, cardiovascular risk, cholesterol
in
American Journal of Transplantation
volume
5
issue
1
pages
87 - 95
publisher
Wiley-Blackwell
external identifiers
  • wos:000225790600011
  • pmid:15636615
  • scopus:19944427631
ISSN
1600-6135
DOI
10.1111/j.1600-6143.2004.00638.x
language
English
LU publication?
yes
id
c7c1bcd8-d0bd-4d4e-817d-cbc79296c5b6 (old id 897740)
date added to LUP
2008-01-21 12:57:59
date last changed
2017-09-03 03:53:12
@article{c7c1bcd8-d0bd-4d4e-817d-cbc79296c5b6,
  abstract     = {Modern immunosuppressive regimens reduce the acute rejection rate by combining a cornerstone immunosuppressant like tacrolimus or cyclosporine with adjunctive agents like corticosteroids, mycophenolate mofetil (MMF) or azathioprine, often associated with untoward side effects. A 6-month randomized study was conducted in 47 European centers. Triple therapy with tacrolimus (trough levels 5-15 ng/mL), corticosteroids (dosage 10 mg/day) and MMF (1 g/day) was administered for 3 months. From day 92, patients either continued with triple therapy (control, n = 277), or stopped steroids (n = 279), or stopped MMF (n = 277). Surrogate markers for long-term benefits were changes in lipid profiles and occurrence of hematological, gastrointestinal and infectious complications. The 6-month acute rejection incidence (biopsy-proven) was similar in all groups (17.0% vs. 15.1% vs. 14.8%, p = 0.744), although the incidence after month 3 was higher in the steroid stop group than in the two other groups. Mean reductions in total cholesterol (18.9 mg/dL [0.49 mmol/L]) and LDL-cholesterol (8.1 mg/dL [0.21 mmol/L]) between months 4 and 6 were greater in the steroid stop group (p &lt; 0.001). Leukopenia (p = 0.0082), serious CMV infection (p = 0.024), anemia (p = NS) and diarrhea (p = NS) were less frequent in the MMF stop group. In a study population of immunologically low-risk patients' withdrawal of corticosteroids or MMF from a tacrolimus-based therapy at 3 months was feasible. A longer follow-up will be needed to confirm the expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.},
  author       = {Vanrenterghem, Y and van Hooff, JP and Squifflet, JP and Salmela, K and Rigotti, P and Jindal, RM and Pascual, J and Ekberg, Henrik and Sicilia, LS and Boletis, JN and Grinyo, JM and Rodriguez, MA},
  issn         = {1600-6135},
  keyword      = {tacrolimus,MMF withdrawal,minimization of immunosuppression,transplantation,kidney,corticosteroid withdrawal,cardiovascular risk,cholesterol},
  language     = {eng},
  number       = {1},
  pages        = {87--95},
  publisher    = {Wiley-Blackwell},
  series       = {American Journal of Transplantation},
  title        = {Minimization of immunosuppressive therapy after renal transplantation: Results of a randomized controlled trial},
  url          = {http://dx.doi.org/10.1111/j.1600-6143.2004.00638.x},
  volume       = {5},
  year         = {2005},
}