Everolimus-Incorporated Immunosuppressant Strategy Improves Renal Dysfunction While Maintaining Low Rejection Rates After Heart Transplantation in Japanese Patients

Teruhiko Imamura; Koichiro Kinugawa; Minoru Ono; Yukie Kagami; Miyoko Endo; Shun Minatsuki; Hironori Muraoka; Naoko Kato; Toshiro Inaba; Hisataka Maki; Masaru Hatano; Atsushi Yao; Shunei Kyo; Issei Komuro

doi:10.1536/ihj.54.222

Clinical Studies

Everolimus-Incorporated Immunosuppressant Strategy Improves Renal Dysfunction While Maintaining Low Rejection Rates After Heart Transplantation in Japanese Patients

Teruhiko Imamura, Koichiro Kinugawa, Minoru Ono, Yukie Kagami, Miyoko Endo, Shun Minatsuki, Hironori Muraoka, Naoko Kato, Toshiro Inaba, Hisataka Maki, Masaru Hatano, Atsushi Yao, Shunei Kyo, Issei Komuro

Author information

Teruhiko Imamura
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Koichiro Kinugawa
Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, The University of Tokyo
Minoru Ono
Department of Cardiothoracic Surgery, Graduate School of Medicine, The University of Tokyo
Yukie Kagami
Department of Organ Transplantation, Graduate School of Medicine, The University of Tokyo
Miyoko Endo
Department of Organ Transplantation, Graduate School of Medicine, The University of Tokyo
Shun Minatsuki
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Hironori Muraoka
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Naoko Kato
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Toshiro Inaba
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Hisataka Maki
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Masaru Hatano
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Atsushi Yao
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
Shunei Kyo
Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, The University of Tokyo
Issei Komuro
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo

Keywords: Renal function, Mycophenolate mophetil, Calcineurin inhibitor

JOURNAL FREE ACCESS

2013 Volume 54 Issue 4 Pages 222-227

DOI https://doi.org/10.1536/ihj.54.222

Details

Abstract

The long-term survival of heart transplantation (HTx) recipients has increased significantly in recent years, however, the nephrotoxic adverse effects of calcineurin inhibitors (CNIs) are still a major concern. Recently, an inhibitor of mammalian target of rapamycin, everolimus (EVL), has emerged as an alternative immunosuppressant drug that may allow CNI dosage reduction and thereby spare renal function. Data were collected from 20 HTx recipients who had received EVL (target trough level 3-8 ng/mL) along with a dose reduction of CNIs and/or mycophenolate mophetil (MMF) and had been followed for 1 year. Estimated glomerular filtration rate increased significantly with a reduction in the CNI dosage in a dose-dependent manner (P < 0.001, r = -0.807). Neutrophil count increased significantly (P < 0.05) with a reduction in the dosage of MMF (P = 0.009, r = -0.671). Cytomegalovirus antigenemia remained negative after EVL administration among all candidates without any antiviral agents (P = 0.001). There were no significant increases in the acute rejection rates among recipients with EVL compared to those without EVL (P = 0.132). An immunosuppressant strategy incorporating EVL could reduce the CNI and MMF dosages, which resulted in improvements in renal dysfunction and neutropenia while maintaining low rejection rates among HTx recipients.

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