Everolimus-incorporated immunosuppressant strategy improves renal dysfunction while maintaining low rejection rates after heart transplantation in Japanese patients.
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.
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
Teruhiko
T
Imamura
Koichiro
K
Kinugawa
Minoru
M
Ono
Yukie
Y
Kagami
Miyoko
M
Endo
Shun
S
Minatsuki
Hironori
H
Muraoka
Naoko
N
Kato
Toshiro
T
Inaba
Hisataka
H
Maki
Masaru
M
Hatano
Atsushi
A
Yao
Shunei
S
Kyo
Issei
I
Komuro
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents; D002648:Child; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology*; D016027:Heart Transplantation / Q000401:mortality*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus