Reduced exposure to calcineurin inhibitors in renal transplantation.
(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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- author
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 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
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- pmid:18094377
- scopus:37349034394
- pmid:18094377
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa067411
- language
- English
- LU publication?
- yes
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- aa04283e-d7c9-4510-af77-c47a4bcc577b (old id 1035046)
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- date added to LUP
- 2016-04-04 07:50:45
- date last changed
- 2022-04-23 08:23:53
@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}},
keywords = {{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}},
doi = {{10.1056/NEJMoa067411}},
volume = {{357}},
year = {{2007}},
}