Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation

J Heart Lung Transplant. 2010 Jun;29(6):641-7. doi: 10.1016/j.healun.2010.01.005. Epub 2010 Mar 20.

Abstract

Background: Calcineurin inhibitor (CNI)-induced nephrotoxicity is a feared adverse effect after heart transplantation (HTx). In patients with advanced renal failure we performed an overnight conversion from cyclosporine (CsA) to everolimus within the first year after HTx and compared changes in renal function to a similar switch performed in a group of long-term HTx survivors with 24-month follow up.

Methods: Sixteen HTx recipients (Group 1), including 5 patients undergoing dialysis, were switched overnight from CsA to everolimus at 5.5 (range 1.3 to 8.5) months post-operatively, whereas 15 patients completed 24 months of follow-up. Fifteen long-term survivors (Group 2) were recruited at 96 (58 to 148) months post-HTx. Due to 3 withdrawals and 2 deaths, 10 of these 15 patients remained available for follow-up assessment.

Results: In Group 1 patients, creatinine level improved from 211 (186 to 263) to 112 (98 to 140) mumol/liter and estimated glomerular filtration rate (eGFR) from 29 (20 to 35) to 62 (43 to 69) ml/min/1.73 m(2) (p < 0.001). In Group 2, creatinine decreased from 227 (188 to 255) to 193 (150 to 250) micromol/liter (p = 0.299), and eGFR increased from 26 (21 to 31) to 28 (22 to 35) ml/min/1.73 m(2) (p = 0.225). Four cellular rejections were treated successfully in Group 1. All together, 24 adverse events occurred.

Conclusions: These preliminary data are the first to suggest that the improvement in renal function after switching to CNI-free everolimus treatment has the greatest potential within the first year post-HTx. While we await randomized, controlled trials, it appears that conversion can be performed with acceptable safety in selected patients.

Publication types

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

MeSH terms

  • Calcineurin Inhibitors*
  • Creatinine / blood
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Everolimus
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / epidemiology
  • Graft Rejection / therapy
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Postoperative Period
  • Recovery of Function
  • Retreatment
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survivors
  • Time Factors

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Creatinine
  • Sirolimus