title: Calcineurin inhibitors: 40 years later, can't live without ...
abstract: Calcineurin inhibitors (CNIs) revolutionized the field of organ transplantation and remain the standard of care 40 years after the discovery of cyclosporine. The early impressive results of cyclosporine in kidney transplant recipients led to its subsequent use in other organ transplant recipients and for treatment of a variety of autoimmune diseases as well. In this review, we examine the discovery of CNIs, their mechanism of action, preclinical and clinical studies with CNIs, and the usage of CNIs in nontransplant recipients. We review the mechanisms of renal toxicity associated with CNIs and the recent efforts to avoid or reduce usage of these drugs. Although minimization strategies are possible, safe, and of potential long-term benefit, complete avoidance of CNIs has proven to be more challenging than initially thought.
authors: Renal Division, Transplantation Research Center, Brigham and Women's Hospital and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
authors: Jamil R
authors: JR
authors: Azzi
authors: Mohamed H
authors: MH
authors: Sayegh
authors: Samir G
authors: SG
authors: Mallat
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000009:adverse effects / Q000737:chemistry / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005544:Forecasting; D006084:Graft Rejection / Q000517:prevention & control; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000737:chemistry / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D016030:Kidney Transplantation / Q000266:history; D008213:Lymphocyte Activation / Q000187:drug effects; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000009:adverse effects / Q000737:chemistry / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus