Everolimus-incorporated immunosuppressant strategy improves renal dysfunction while maintaining low rejection rates after heart transplantation in Japanese patients

Int Heart J. 2013;54(4):222-7. doi: 10.1536/ihj.54.222.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents
  • Child
  • Dose-Response Relationship, Drug
  • Everolimus
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects*
  • Graft Rejection / drug therapy
  • Graft Rejection / epidemiology*
  • Heart Transplantation / mortality*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Practice Guidelines as Topic*
  • Renal Insufficiency / etiology
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / prevention & control*
  • Retrospective Studies
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survival Rate / trends
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Everolimus
  • Mycophenolic Acid
  • Sirolimus