Aim: To follow up (FU) on the evolution of renal function (RF) of immunosuppressive regimens with different calcineurin inhibitor (CNI) exposure at month (Mo)24 post renal transplantation (Tx).
Methods: 802 patients (pts) were included in this 1year, prospective, open-label, randomized (rdz), and controlled multi-center study. After induction with basiliximab all pts received cyclosporine A (CsA), enteric-coated mycophenolate sodium (EC-MPS) and steroids. 3Mo post Tx 499 pts were rdz 1:1:1 to either a) continue standard (STD) CsA(100-180ng/ml) with EC-MPS (n=166), b) convert to a CNI-free regimen with everolimus (EVE;5-10ng/ml) and EC-MPS (n=171) or c) convert to CNI-low regimen with EVE(3-8ng/ml) and reduced CsA(50-75ng/ml) (n=162). Mo24 FU visit was performed by 131(95.6%) STD, 132(95.7%) CNI-free and 125(92.6%) CNI-low pts. RF was assessed by Glomerular Filtration Rate (cGFR; Nankivell) as primary endpoint.
Results: CsA trough level was 99±32ng/ml in STD, 83±34ng/ml in CNI-low pts. EVE trough level was 6.7±3.1ng/ml in CNI-free, 6.2±2.3ng/ml in CNI-low pts. RF was similar at rdz 3 Mo post Tx and had significantly improved at Mo12 by +5.6mL/min/1.73m2(95%CI:[+2.9;+8.3];p<0.001) in favor of the CNI-free regimen and remained significantly improved by +4.8mL/min/1.73m2(95%CI:[+1.0;+8.6]) in favor of the CNI-free regimen at Mo24(ITT;p=0.014).
|eGFR (Nankivell) [ml/min/1.73m2||N||LS-Mean [95%CI] ANCOVA LOCF Mo24||Difference vs. Standard [95%CI]||p-value vs. Standard|
|CNI-free||98||68.3 [65.0;71.7]||4.8 [1.0;8.6]||0.0141|
|CNI-low||97||63.4 [60.1;66.8]||-0.1 [-3.9;3.7]||0.9557|
Result of RF were confirmed by other formulas. 65.0% of CNI-free, 51.5% of CNI-low and 57.9% of STD pts had an improvement in RF at Mo24. All three groups had similar rejection rate since rdz (11.8% STD, 13.7% CNI-free, 12.1% CNI-low) with overall comparable safety profile.
Conclusion: The profound reduction of CsA in combination with EVE did not result in better RF compared to STD therapy with EC-MPS whereas CNI-free regimen lead to better RF maintained for 2years. The results of this large trial confirm previous reports of an improved RF after CsA withdrawal with EVE in combination with EC-MPS.
Budde, K.: Other, Novartis, Research Funds and/or Trial Honoraria, Roche, Research Funds and/or Trial Honoraria, Pfizer, Research Funds and/or Trial Honoraria, Astellas, Research Funds and/or Trial Honoraria, Bristol-Myers Squibb, Research Funds and/or Trial Honoraria, Hexal, Research Funds and/or Trial Honoraria. Arns, W.: Other, Novartis, Study Honoraria, Roche, Study Honoraria, Pfizer, Study Honoraria, Astellas, Study Honoraria. Sommerer, C.: Other, Novartis, Honoraria, Astellas, Honoraria. Lehner, F.: Other, Novartis, Speakers and Consultancy Fee, Research Fund, Astellas, Speakers and Consultancy Fee, Research Fund, BMS, Speakers and Consultancy Fee, Research Fund, Roche, Speakers and Consultancy Fee, Research Fund. Zeier, M.: Other, Novartis, Speakers Fee, Honoraria, Research Grant, Bristol-Myers Squibb, Speakers Fee, Honoraria, Fresenius Medical Care, Speakers Fee, Honoraria, Abbott, Speakers Fee, Honoraria, Medronic Vascular Inc. Speakers Fee, Honoraria. Neumayer, H.: Grant/Research Support, Astellas, Roche, Fresenius, Other, Novartis, Research Funds and Honoraria, Bristol-Myers Squibb, Honoraria, Alexion, Honoraria. Guba, M.: Grant/Research Support, Novartis, Other, Astellas, Travel Grant. Jacobi, J.: Grant/Research Support, Novartis. Weithofer, P.: Grant/Research Support,
To cite this abstract in AMA style:Budde K, Arns W, Sommerer C, Lehner F, Zeier M, Neumayer H, Guba M, Jacobi J, Weithofer P, May C, Baeumer D, Paulus E, Witzke O. Superior Renal Function in an Everolimus-Based Calcineurin Inhibitor Free Regimen Compared to Standard Cyclosporine/Mycophenolate and Low Cyclosporine/Everolimus: Follow-Up of the HERAKLES Study at Month 24 [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/superior-renal-function-in-an-everolimus-based-calcineurin-inhibitor-free-regimen-compared-to-standard-cyclosporinemycophenolate-and-low-cyclosporineeverolimus-follow-up-of-the-herakles-study-at-mo-2/. Accessed March 3, 2021.
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