Section of Nephrology, Division of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, Texas, USA.
Nephron. 2024;148(1):11-15. doi: 10.1159/000531297. Epub 2023 May 31.
The clinical indications for immune checkpoint inhibitors (ICIs) are rapidly expanding. However, adverse events affecting multiple organs, including kidneys leading to ICI-associated acute kidney injury (AKI), remain a significant challenge with ICI therapy. Although AKI is considered a rare complication, it can be severe and result in treatment interruption or discontinuation of ICIs. Despite a generally favorable kidney prognosis, the possibility of re-challenging ICI therapy remains a subject of debate, particularly for patients who have exhausted other treatment options or experienced severe AKI. Subject of Review: In a recent review article, Sprangers et al. provide a comprehensive overview of the possible mechanisms and clinical manifestations of ICI-associated AKI [Nat Rev Nephrol. 2022;18(12):794-805]. The authors propose a practical strategy for diagnosing and managing suspected cases of ICI-associated AKI, which includes identifying a subset of eligible patients who may be re-exposed to ICIs following an episode of AKI. Second Opinion: The authors of the review article offer several recommendations on the diagnosis and treatment of ICI-associated nephrotoxicity. While we generally agree with the recommendations proposed by the authors, it is important to acknowledge that the available data primarily rely on small retrospective studies, as the authors have recognized. In addition, there are two key questions that need be carefully addressed in future studies: (1) the optimal dose and duration of corticosteroids and the use of alternative immunosuppressive agents in patients with ICI-associated nephrotoxicity and (2) a clear guideline for restarting ICI treatment in patients with AKI who have not fully recovered their kidney function.
免疫检查点抑制剂(ICIs)的临床适应证正在迅速扩大。然而,影响多个器官的不良反应,包括导致免疫检查点抑制剂相关急性肾损伤(AKI)的肾脏问题,仍然是 ICI 治疗的一个重大挑战。尽管 AKI 被认为是一种罕见的并发症,但它可能很严重,并导致治疗中断或停止 ICI 治疗。尽管一般来说肾脏预后良好,但重新挑战 ICI 治疗的可能性仍然存在争议,特别是对于已经用尽其他治疗选择或经历过严重 AKI 的患者。综述主题:在最近的一篇综述文章中,Sprangers 等人提供了对免疫检查点抑制剂相关 AKI 的可能机制和临床表现的全面概述[Nat Rev Nephrol. 2022;18(12):794-805]。作者提出了一种用于诊断和管理疑似免疫检查点抑制剂相关 AKI 的实用策略,其中包括确定一组符合条件的患者,这些患者在经历 AKI 后可能会重新暴露于 ICI 下。第二意见:该综述文章的作者就免疫检查点抑制剂相关肾毒性的诊断和治疗提出了一些建议。虽然我们基本同意作者提出的建议,但需要承认的是,正如作者所认识到的,现有数据主要依赖于小型回顾性研究。此外,未来研究中还需要仔细解决两个关键问题:(1)在免疫检查点抑制剂相关肾毒性患者中,皮质类固醇的最佳剂量和持续时间以及替代免疫抑制剂的使用;(2)在未完全恢复肾功能的 AKI 患者中,明确重新开始 ICI 治疗的指南。