Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?

Int J Cardiol. 2014 Jan 15;171(1):15-23. doi: 10.1016/j.ijcard.2013.11.036. Epub 2013 Nov 23.

Abstract

Background: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i.

Methods: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences.

Results: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07).

Conclusion: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Keywords: Cardiac transplantation; Everolimus; Immunosuppression; Renal function; Sirolimus.

Publication types

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

MeSH terms

  • Aged
  • Calcineurin / metabolism
  • Calcineurin Inhibitors*
  • Cohort Studies
  • Drug Substitution* / trends
  • Everolimus
  • Female
  • Follow-Up Studies
  • Heart Transplantation* / trends
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / metabolism
  • Renal Insufficiency / surgery
  • Retrospective Studies
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Calcineurin
  • Sirolimus