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Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate

Arora, Satish; Gude, Einar; Sigurdardottir, Vilborg; Mortensen, Svend Aage; Eiskjaer, Hans; Riise, Gerdt; Mared, Lena LU ; Bjortuft, Oystein; Ekmehag, Björn LU and Jansson, Kjell, et al. (2012) In The Journal of Heart and Lung Transplantation 31(3). p.259-265
Abstract
BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. METHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. RESULTS: In... (More)
BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. METHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. RESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p < 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. CONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus. J Heart Lung Transplant 2012;31:259-65 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved. (Less)
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published
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keywords
thoracic transplantation, heart and lung transplantation, everolimus, CNI reduction, renal failure, GFR improvement
in
The Journal of Heart and Lung Transplantation
volume
31
issue
3
pages
259 - 265
publisher
Elsevier
external identifiers
  • wos:000300806500006
  • scopus:84856872316
ISSN
1557-3117
DOI
10.1016/j.healun.2011.12.010
language
English
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yes
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6d9ea2af-36a3-48de-b670-798fac223b67 (old id 2390831)
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2012-04-02 09:25:26
date last changed
2017-11-05 03:23:54
@article{6d9ea2af-36a3-48de-b670-798fac223b67,
  abstract     = {BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. METHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. RESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p &lt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. CONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus. J Heart Lung Transplant 2012;31:259-65 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.},
  author       = {Arora, Satish and Gude, Einar and Sigurdardottir, Vilborg and Mortensen, Svend Aage and Eiskjaer, Hans and Riise, Gerdt and Mared, Lena and Bjortuft, Oystein and Ekmehag, Björn and Jansson, Kjell and Simonsen, Svein and Aukrust, Pal and Solbu, Dag and Iversen, Martin and Gullestad, Lars},
  issn         = {1557-3117},
  keyword      = {thoracic transplantation,heart and lung transplantation,everolimus,CNI reduction,renal failure,GFR improvement},
  language     = {eng},
  number       = {3},
  pages        = {259--265},
  publisher    = {Elsevier},
  series       = {The Journal of Heart and Lung Transplantation},
  title        = {Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate},
  url          = {http://dx.doi.org/10.1016/j.healun.2011.12.010},
  volume       = {31},
  year         = {2012},
}