Minireviews
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplantation. Sep 10, 2018; 8(5): 150-155
Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.150
Introduction of everolimus in kidney transplant recipients at a late posttransplant stage
Junji Uchida, Tomoaki Iwai, Tatsuya Nakatani
Junji Uchida, Tomoaki Iwai, Tatsuya Nakatani, Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Author contributions: Uchida J, Iwai T and Nakatani T contributed equally to this work, generated the tables and wrote the manuscript.
Conflict-of-interest statement: We have no personal or financial interests to declare, and we have no financial support from an industry source for the current manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Junji Uchida, MD, PhD, Associate Professor, Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3, Abeno-ku, Asahi-machi, Osaka 545-8585, Japan. m9492120@msic.med.osaka-cu.ac.jp
Telephone: +81-6-66453857 Fax: +81-6-66474426
Received: May 21, 2018
Peer-review started: May 21, 2018
First decision: June 6, 2018
Revised: June 23, 2018
Accepted: June 27, 2018
Article in press: June 28, 2018
Published online: September 10, 2018
Processing time: 109 Days and 4.2 Hours
Abstract

This minireview focuses on the current knowledge about the introduction of everolimus (EVL), a mammalian target of rapamycin inhibitor, with calcineurin inhibitor (CNI) elimination or minimization in kidney transplant recipients at a late posttransplant stage. Within, we have summarized two major clinical trials, ASCERTAIN and APOLLO, and seven other retrospective or nonrandomized studies. In the open-label multicenter ASCERTAIN study, the estimated glomerular filtration rate (eGFR) at 24 mo after conversion was not significantly different between three groups-EVL with CNI elimination, CNI minimization and continued CNI unchanged-at a mean of 5.4 years after transplantation. However, recipients with baseline creatinine clearance higher than 50 mL/min had a greater increase in measured GFR after CNI elimination. In the open-label multicenter APOLLO study, adjusted eGFR within the on-treatment population was significantly higher in the EVL continuation group than in the CNI continuation group at 12 mo after conversion at a mean of 7 years posttransplantation. Other studies on recipients without adverse events and already having satisfactory renal function showed favorable graft function by EVL late-induction with CNI elimination or reduction. These studies showed that chronic allograft nephropathy, CNI nephrotoxicity, CNI arteriolopathy, cancer and viral infection (especially cytomegalovirus infection) may be good indications for late conversion to EVL.

Keywords: Kidney transplantation; Everolimus; mTOR inhibitor; Late conversion; Calcineurine inhibitor

Core tip: Current immunosuppressive protocols consisting of calcineurin inhibitors (CNIs) and mycophenolate mofetil have improved short-term graft survival. However, improvements in long-term graft survival are restricted by nephrotoxicity associated with CNI. Everolimus is an exceedingly useful immunosuppressant for kidney transplant recipients when administered in combination with low-dose CNIs or with elimination of CNIs. Here, we summarize the current knowledge about the introduction of everolimus with CNI elimination or minimization in kidney transplant recipients at late posttransplant stage.