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

Abstract

SummaryThe 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. (Int Heart J 2013; 54: 222-227)

Everolimus Attenuates Myocardial Hypertrophy and Improves Diastolic Function in Heart Transplant Recipients

“…13) CNI-minimization or free regimens plus EVL have advantages in terms of the improvement of renal function among heart or renal transplantation recipients, and EVL-incorporated regimens have recently been increasing. [16][17][18][19][20] Recent clinical studies including ours also demonstrated the suppressive effects of EVL in cardiac allograft vasculopathy and post-transplant malignancy. [21][22][23][24][25] Considering that both SRL and EVL are mTOR inhibitors, EVL may also have a repressive effect on LVM.…”

“…[13][14][15] However, little is known about how the next generation mTOR inhibitor derivative everolimus (EVL) affects LVM. 13,16,17) EVL has become thus far a major mTOR inhibitor for immunosuppression therapy because of its superiority in terms of fewer adverse effects compared to SRL. 13) CNI-minimization or free regimens plus EVL have advantages in terms of the improvement of renal function among heart or renal transplantation recipients, and EVL-incorporated regimens have recently been increasing.…”

How Should We Treat Early Post-Transplant Lymphoproliferative Disease After Heart Transplantation?

“…The new immunosuppressant EVL, which is a mammalian target of rapamycin, has recently been demonstrated to have various advantages in terms of its prophylactic effect of CMV infection, 8,13) suppressive effect of cardiac allograft vasculopathy, [14][15][16] anti-malignancy effect, 17,18) and maintenance of renal function, 19) and subsequently its use has increased around the world. Although EVL has been reported to have a prophylactic effect towards PTLD, 18) it may not necessarily protect the development of early-PTLD completely considering the findings in the present patient.…”

Parasympathetic Reinnervation Accompanied by Improved Post-Exercise Heart Rate Recovery and Quality of Life in Heart Transplant Recipients

“…10) Immunosuppression regimen consisted of cyclosporine, or tacrolimus, mycophenolate mophetil, and/or everolimus with low dose prednisolone as described in our previous study. 7,11) All patients had sinus rhythm, and anyone with arrhythmias or mechanical pacing was excluded. All patients gave informed consent before their enrollment in the study.…”