title: Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients.
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.
authors.affiliation: Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Eppendorf, Hamburg, Germany. nashan@uke.de
authors.forename: Björn
authors.initials: B
authors.lastname: Nashan
mesh_terms: D019703:Calcineurin / Q000737:chemistry*; D006084:Graft Rejection / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007674:Kidney Diseases / Q000150:complications* / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin
keywords: antithymocyte globulin; basiliximab; calcineurin inhibitors; daclizumab; everolimus; induction; kidney transplantation; mTOR inhibitors; minimization; sirolimus