Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients

Clin Transplant. Jul-Aug 2013;27 Suppl 25:16-29. doi: 10.1111/ctr.12156.

Abstract

Use of induction therapy with mTOR inhibitor maintenance immunosuppression to facilitate reduced calcineurin inhibitor (CNI) exposure in de novo kidney transplant patients has been explored in a series of randomized trials. These studies have typically employed interleukin-2 receptor antagonist (IL-2RA) induction, in low or standard immunological risk recipients. Although no study has directly compared mTOR inhibition plus reduced CNI exposure with or without induction, inclusion of IL-2RA induction appears to permit a substantial reduction in CNI exposure without the need for high mTOR inhibitor dosing. IL-2RA induction with an mTOR inhibitor and steroids has consistently shown similar efficacy to standard-exposure CNI with mycophenolic acid and steroids and may improve renal function among patients who remain on the mTOR inhibitor-based regimen. With modern mTOR inhibitor dosing, wound healing complications are of less concern and may be no more frequent than in mycophenolic acid-based regimens. The incidence of cytomegalovirus infection appears lower in patients receiving de novo mTOR inhibition. The available evidence demonstrates that IL-2RA induction with an mTOR inhibitor can successfully reduce CNI exposure by at least half without a penalty in terms of rejection in low- or moderate-risk de novo transplant recipients and may offer renal and antiviral benefits.

Keywords: antithymocyte globulin; basiliximab; calcineurin inhibitors; daclizumab; everolimus; induction; kidney transplantation; mTOR inhibitors; minimization; sirolimus.

MeSH terms

  • Calcineurin / chemistry*
  • Graft Rejection / chemically induced
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Kidney Diseases / complications*
  • Kidney Diseases / surgery
  • Kidney Transplantation / adverse effects*
  • Postoperative Complications*
  • Randomized Controlled Trials as Topic
  • Remission Induction
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Calcineurin