Renal Division, Transplantation Research Center, Brigham and Women's Hospital and Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
J Immunol. 2013 Dec 15;191(12):5785-91. doi: 10.4049/jimmunol.1390055.
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.
钙调磷酸酶抑制剂（CNIs）彻底改变了器官移植领域，在环孢素发现 40 年后仍然是护理标准。环孢素在肾移植受者早期令人印象深刻的结果导致其随后在其他器官移植受者中使用，并用于治疗各种自身免疫性疾病。在这篇综述中，我们检查了 CNI 的发现、它们的作用机制、CNI 的临床前和临床研究，以及 CNI 在非移植受者中的使用。我们回顾了与 CNI 相关的肾毒性机制，以及最近避免或减少使用这些药物的努力。尽管最小化策略是可能的、安全的且具有潜在的长期益处，但事实证明，完全避免 CNI 比最初想象的更具挑战性。
