Fernando Mangalee, Peake Philip W, Endre Zoltan H
Department of Nephrology, Prince of Wales Hospital, Barker St., Randwick, Sydney, NSW, Australia.
Biomark Med. 2014;8(10):1247-62. doi: 10.2217/bmm.14.86.
Over 35 years of use has demonstrated the revolutionary therapeutic benefits of calcineurin inhibitors (CNI) in not only preventing transplant rejection, but also the renal and nonrenal toxicity of CNI. Acute reversible and insidious irreversible forms of CNI nephrotoxicity have been identified, with ischemia from an imbalance between vasoconstrictors and vasodilators playing an important role. The ongoing search to define toxicity pathways has been enriched by 'Omics' studies. Changes in proteins including those involved in activation of pro-inflammatory responses, oxidative stress, ER stress and the unfolded protein response have been identified, and these may serve as biomarkers of toxicity. However, the current standard of CNI toxicity, histology, lacks specificity, which creates challenges for biomarker validation. This review focuses on progress in nephrotoxic pathway identification of CNI and biomarker validation.
超过35年的使用已证明钙调神经磷酸酶抑制剂（CNI）具有革命性的治疗益处，不仅能预防移植排斥反应，还能预防CNI的肾毒性和非肾毒性。已识别出CNI肾毒性的急性可逆和隐匿性不可逆形式，血管收缩剂和血管舒张剂失衡导致的缺血起重要作用。 “组学”研究丰富了对毒性途径的持续探索。已识别出蛋白质变化，包括参与促炎反应激活、氧化应激、内质网应激和未折叠蛋白反应的蛋白质变化，这些可能作为毒性生物标志物。然而，目前CNI毒性的标准——组织学缺乏特异性，这给生物标志物验证带来了挑战。本综述重点关注CNI肾毒性途径识别和生物标志物验证方面的进展。
