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Reduced exposure to calcineurin inhibitors in renal transplantation.

Ekberg, Henrik LU ; Tedesco-Silva, Helio; Demirbas, Alper; Vítko, Stefan; Nashan, Björn; Gürkan, Alp; Margreiter, Raimund; Hugo, Christian; Grinyó, Josep M and Frei, Ulrich, et al. (2007) In New England Journal of Medicine 357(25). p.2562-2575
Abstract
BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS:... (More)
BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].). (Less)
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Adrenal Cortex Hormones: administration & dosage, Adrenal Cortex Hormones: therapeutic use, Antibodies, Monoclonal: administration & dosage, Calcineurin: antagonists & inhibitors, Cyclosporine: administration & dosage, Diabetes Mellitus: etiology, Graft Rejection: prevention & control, Enzyme Inhibitors: administration & dosage, Immunoglobulin G: administration & dosage, Immunosuppressive Agents: adverse effects, Immunosuppressive Agents: administration & dosage, Immunosuppressive Agents: therapeutic use, Mycophenolic Acid: analogs & derivatives, Mycophenolic Acid: administration & dosage, Prednisone: administration & dosage, Sirolimus: administration & dosage, Sirolimus: adverse effects, Tacrolimus: administration & dosage
in
New England Journal of Medicine
volume
357
issue
25
pages
2562 - 2575
publisher
Massachusetts Medical Society
external identifiers
  • pmid:18094377
  • scopus:37349034394
ISSN
0028-4793
DOI
10.1056/NEJMoa067411
language
English
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yes
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aa04283e-d7c9-4510-af77-c47a4bcc577b (old id 1035046)
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http://www.ncbi.nlm.nih.gov/pubmed/18094377?dopt=Abstract
date added to LUP
2008-02-29 13:11:42
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2017-11-12 04:07:01
@article{aa04283e-d7c9-4510-af77-c47a4bcc577b,
  abstract     = {BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).},
  author       = {Ekberg, Henrik and Tedesco-Silva, Helio and Demirbas, Alper and Vítko, Stefan and Nashan, Björn and Gürkan, Alp and Margreiter, Raimund and Hugo, Christian and Grinyó, Josep M and Frei, Ulrich and Vanrenterghem, Yves and Daloze, Pierre and Halloran, Philip F},
  issn         = {0028-4793},
  keyword      = {Adrenal Cortex Hormones: administration & dosage,Adrenal Cortex Hormones: therapeutic use,Antibodies,Monoclonal: administration & dosage,Calcineurin: antagonists & inhibitors,Cyclosporine: administration & dosage,Diabetes Mellitus: etiology,Graft Rejection: prevention & control,Enzyme Inhibitors: administration & dosage,Immunoglobulin G: administration & dosage,Immunosuppressive Agents: adverse effects,Immunosuppressive Agents: administration & dosage,Immunosuppressive Agents: therapeutic use,Mycophenolic Acid: analogs & derivatives,Mycophenolic Acid: administration & dosage,Prednisone: administration & dosage,Sirolimus: administration & dosage,Sirolimus: adverse effects,Tacrolimus: administration & dosage},
  language     = {eng},
  number       = {25},
  pages        = {2562--2575},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Reduced exposure to calcineurin inhibitors in renal transplantation.},
  url          = {http://dx.doi.org/10.1056/NEJMoa067411},
  volume       = {357},
  year         = {2007},
}