Wiseman Alexander C
Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado, Denver, Aurora, Colorado
Clin J Am Soc Nephrol. 2016 Feb 5;11(2):332-43. doi: 10.2215/CJN.08570814. Epub 2015 Jul 13.
Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.
免疫抑制剂在肾脏病医生的临床实践中常用于治疗自身免疫性疾病、免疫介导性疾病以及移植相关疾病,目前也正处于治疗急性肾损伤(AKI)和终末期肾病(ESRD)的研究阶段。在过去几十年中,随着免疫反应机制通过意外发现(发现具有免疫抑制活性的药物从而加深了对免疫反应的理解)和机制性研究(对免疫缺陷、自身免疫性疾病以及导致疾病的关键途径或突变的研究)得到了更清晰的界定,药物研发进展迅速。早期免疫抑制剂,如皮质类固醇、硫唑嘌呤和环磷酰胺的毒性促使人们对具有更高特异性和更低有害作用的药物展开深入研究。由于在过去30年中免疫反应机制得到了更清晰的阐述,如今该领域拥有众多治疗选择,这些选择降低了肾移植中的排斥率并提高了移植物存活率,为免疫介导性疾病中的细胞毒性治疗提供了替代方案,还为常见疾病(AKI)和罕见疾病(非典型溶血性综合征)的干预开辟了新机会。本综述的目的并非总结所有现有免疫抑制药物的临床适应证和临床试验,而是将这些药物置于机制背景下,并简要讨论肾脏病医生感兴趣的药物研发与使用的独特特征。