Childhood & Adolescent Hematology Oncology Unit, 2nd Pediatric Department, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital, Greece.
Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital Münster, Münster, Germany.
Expert Opin Drug Saf. 2021 Sep;20(9):1061-1074. doi: 10.1080/14740338.2021.1922667. Epub 2021 Jun 1.
Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades have seen a considerable expansion in antifungal drug research, resulting in the clinical development of different classes of antifungal agents with different pharmacologic properties. Among drug-specific characteristics of antifungal agents, renal disposition and nephrotoxicity are important clinical considerations as many patients requiring antifungal therapy have compromised organ functions or are receiving other potentially nephrotoxic medications.
The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies.
Based on the available data amphotericin B deoxycholate has the highest relative potential for nephrotoxicity, followed by the lipid formulations of amphotericin B, and, to a much lesser extent and by indirect mechanisms, the antifungal triazoles.
侵袭性真菌感染仍然是重病和免疫功能低下患者群体发病率和死亡率的重要原因。在过去的三十年中，抗真菌药物的研究有了相当大的扩展，导致了不同类别的具有不同药理特性的抗真菌药物的临床发展。在抗真菌药物的药物特异性特征中，肾脏处置和肾毒性是重要的临床考虑因素，因为许多需要抗真菌治疗的患者的器官功能受损或正在接受其他潜在的肾毒性药物。
本文通过讨论药物安全性数据背景下的分布、代谢、消除和与药物相关的不良事件，回顾了预防和治疗侵袭性真菌感染的抗真菌药物与肾毒性相关的发生率、严重程度和机制。
根据现有数据，两性霉素 B 脱氧胆酸盐具有最高的肾毒性相对潜力，其次是两性霉素 B 的脂质制剂，而三唑类抗真菌药物的肾毒性则要小得多，且通过间接机制。
