title: Immunosuppressive minimization with mTOR inhibitors and belatacept.
abstract: Immunosuppressive therapy after kidney transplantation consists of a calcineurin inhibitor (CNI)-based therapy in combination with mycophenolic acid and steroids in most cases. In spite of low acute rejection rates and excellent graft survival, it is associated with major long-term complications, such as cardiovascular events, malignancy, and nephrotoxicity, and does not favor tolerogenic processes. Mammalian target of rapamycin (mTOR) inhibitors in combination with low-dose CNI offer good rejection rates and acceptable allograft function; however, de novo mTOR inhitibor-based treatment in combination with mycophenolate is not widely used due to higher acute rejection rates. Early conversion from a CNI to an mTOR inhibitor is a feasible option in selected patients with a slightly higher acute rejection rate, but equal or better GFR. Costimulation blockade has been proven to facilitate antirejection prophylaxis without CNI-associated side effects. So far, belatacept has been approved in combination with mycophenolate and steroids with better graft function, however, a slightly higher acute rejection rate. Recently, the combination of an mTOR inhibitor and belatacept with lymphocyte-depleting antibody induction and without maintenance steroids has been explored in two pilot studies with very low acute rejection rates, very good graft function, and an acceptable side effect profile.
authors.affiliation: Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain.
authors.forename: Fritz
authors.initials: F
authors.lastname: Diekmann
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000069594:Abatacept; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: clinical immunosuppression; costimulation blockade; mTOR inhibition