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针对肾功能正常和受损患者的肾癌的靶向治疗的肾毒性。

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function.

机构信息

Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.

Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

出版信息

Cancer Chemother Pharmacol. 2021 Jun;87(6):723-742. doi: 10.1007/s00280-021-04260-y. Epub 2021 Mar 25.

Abstract

The introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.

摘要

在过去的 20 年中,新型靶向治疗药物的引入显著改善了肾癌患者的临床结局。然而,这一改善是以全新的一系列不良反应为代价的,包括肾毒性。对于常伴有肾功能损害的肾肿瘤患者进行全身性治疗,即使在治疗前,也对临床医生提出了越来越大的诊断和治疗挑战。常见的与生活方式相关的合并症,如高血压和糖尿病,可能会进一步损害肾功能。缺乏官方指南以及最近批准的药物临床试验排除了肾功能降低的患者,使问题更加复杂。早期发现和正确处理肾毒性作用对于保护肾功能和确保延长生命的治疗的最佳管理至关重要。这篇综述详细介绍了在肾细胞癌治疗中常用的三组药物的肾毒性:酪氨酸激酶抑制剂、雷帕霉素哺乳动物靶蛋白抑制剂和免疫检查点抑制剂。我们概述了肾不良反应的发生率和潜在机制,重点关注接受肾脏替代治疗的患者,并提出了管理建议。

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